June 2015 Volume XXXIII No 2

insightScientifi c Journal of MEDICAL & VISION RESEARCH FOUNDATIONS

www.sankaranethralaya.org Editor: Parthopratim Dutta Majumder insight

Scientifi c Journal of Medical & Vision Research Foundations Sankara Nethralaya – The Temple of the Eye.

Year: 2015 It was in 1976 when addressing a group of doctors, His Holiness Sri Jayendra Saraswathi, the Sankaracharya of the Kanchi Kamakoti Peetam spoke of the need to create a hospital with a missionary spirit. His words marked the Issue: Vol. XXXIII | No. 2 | June 2015 | Pages 49–113 beginning of a long journey to do God’s own work. On the command of His Holiness, Dr. Sengamedu Srinivasa Badrinath, along with a group of philanthropists founded a charitable not-for-profi t eye hospital. Sankara Nethralaya today has grown into a super specialty institution for ophthalmic care and receives patients from all over the country and abroad. It has gained international excellence and is acclaimed for its quality care and compassion. The Sankara Nethralaya family today has Typeset at: Techset Composition India (P) Ltd., Chennai, India over 1400 individuals with one vision – to propagate the Printed at: Gnanodaya Press, Chennai, India Nethralaya philosophy; the place of our work is an Alaya and Work will be our worship, which we shall do with sincerity, ©Medical and Vision Research Foundations dedication and utmost love with a missionary spirit.

Contents

Guest Editorial: Academics, Research and Clinical Work: the Balancing Act 49 Lingam Gopal Preferred Practice Pattern: Diabetic Macular Edema 50 Rajiv Raman and Muna Bhende Review article: Micro Incision Vitrectomy Surgery (MIVS): An Overview 57 Pramod S. Bhende and Aneesha Lobo Preferred practice pattern: Endophthalmitis: Current Trends, Drugs, and Protocols 61 Aditya Verma, Vinata Muralidharan and Eesh Nigam Recent advances: Macular Buckle in Myopia 71 Pradeep Susvar and S. Vinay Kumar Recent advances: Optical Coherence Tomography: Newer Techniques, Newer Machines 75 KP Mohana, Debmalya Das and Muna Bhende Preferred practice pattern: Intravitreal Injection Guidelines 80 Ekta Rishi and Pramod Bhende Recent advances: Recent Advancements in Ocular Electrodiagnostics 83 Parveen Sen and Ramya Sachidanandam Recent advances: Genetic Testing for Eye Diseases 87 Vikas Khetan Recent advances: Update on Intraocular Oncology 88 Suganeswari Ganesan Review article: Retinopathy of Prematurity: An Update 93 Parveen Sen, Chetan Rao and Nishat Bansal Recent advances: Current Role of Photodynamic Therapy in Ophthalmic Practice 97 Pukhraj Rishi and Vishvesh Agarwal Recent advances: Techniques of Fundus Imaging 100 Amit B. Jain, Vadivelu Jaya Prakash and Muna Bhende Ophthalmic photography: Insight Ophthalmic Photography Competition 108 Jaydeep Avinash Walinjkar and Mohammadarif Mulla Last Word: Developing Clinical Empathy: Enhancing Patients’ Satisfaction Tarun Sharma

Inquiries or comments may be mailed to the editor at [email protected] This special issue of Insight is dedicated to our beloved Chairman Emeritus, Dr SS Badrinath who has completed his joyous journey of 75 years and carved this Fountainhead of Knowledge - the Temple of Eye - SANKARA NETHRALAYA. Guest editorial

Academics, Research and Clinical Work: the Balancing Act

Lingam Gopal

Before we talk about the balan- after it was written, it is still relevant in its Correspondence to: cing act, let us discuss what can message. A great pathologist had to resign in Lingam Gopal, define each of the three activ- ignominy when he fails to keep up with knowl- Senior consultant, edge and makes a blunder. National University Hospital ities that comprise the clini- Singapore cian’s work schedule: clinical Research is like the icing on the proverbial cake. President, work, academics and research. It is mentally stimulating and generates creativity Vision Research Foundation Clinical work can be defined in a person. Even the very act of trying to write a Sankara Nethralaya as the direct interaction with grant application is a huge learning process. A Chennai, India – patients related to the amelioration of their illness. clinician researcher cannot say he/she will not see E-mail: [email protected] This is perhaps the most important reason why we patients but do only research. Where will the ideas have qualified as doctors. Academics can be come from, if one does not see enough clinical defined as acquisition and dissemination of knowl- spectrum of disease? Research does not have to be edge while research can be defined as the delving always in the form of a major project. Small ideas, into the world of unknown or partially known. which can potentially improve the delivery of fi Practice of clinical medicine involves broadly health care or make it more ef cient, can also be speaking, diagnosing the condition, administra- research projects. Interaction between clinicians tion of medical treatment and performing surgical and basic scientists creates a fertile ground for gen- procedures where needed, with compassion as the erating new ideas that can be converted to good- main driving force. Academics as we practice quality research projects. involves interaction with trainees, publishing in Having said that, research can still be optional. peer reviewed journals, presentation in confer- There may be many reasons why a clinician may — ences etc. Research can be purely clinical or a not be able to indulge in research interest or lack combination of clinical and basic science research. of it, available time, priorities etc. At their core however, all the three facets of our Balancing is a part of life in general and functioning would need relevant knowledge, logical equally applicable to the professional life. While thinking, sound judgment and practical experience. one can prioritize what one wants to do and what The knowledge acquired initially through proper one does not want to do, there is one activity, we training and teaching during our formative years as clinicians are committed to do and hence duty — forms a good basic foundation. However, an equal or bound to do i.e. good patient care. To enable this more amount of knowledge is added by constant to be consistently of the highest order, academics updating through journals, conferences, visiting is a must. senior clinicians etc. This acquisition of knowledge We have to run to stay at the same place, lest helps in turn to treat our patients better. One should we are dragged backwards and have a shameful ‘ ’ remember that, in this era of the internet, the patients fall. Often one offers lack of time as an excuse. —‘ can be more informed than the clinicians about the But more often than not improper utilization of ’ most recent developments—since they will be con- time is the cause. One should seriously ask centrating on digging into information on one oneself if the time off from clinical work is prop- disease that they are interested in. erly utilized. Setting long-term goals and short- Academics helps one to keep abreast of latest term targets is a good way of proportioning this developments. The preparation for lectures, inter- academic time and making best use of it. Research action with the trainees, writing articles for jour- (done to any extent) tends to round off the profes- nals, reviewing articles written by others etc. are all sional satisfaction one gets. If one does not want ways of enriching one’s mind. It is not a waste of the icing on the cake, so be it. time nor is it second in its importance to clinical Broadly, one should be able to do justice if care. It is a vital activity to maintain one’stalents 80% of time is allocated for clinical work; 10% as a good clinician. Hence it is not a question of for academics and 10% for research, with the clinics versus academics but clinics and academics proviso that the time is well utilized for the for as long as we are practicing medicine. purpose intended. Finally, one should remember — I would recommend everyone to read the book that there is never enough of what we want by Arthur Hailey, ‘The final diagnosis’. Fifty years money, affection, time, power etc.

How to cite this article Gopal L. Academics, Research and Clinical Work: the Balancing Act, Sci J Med & Vis Res Foun 2015;XXXIII:49.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 49 Preferred Practice Pattern

Diabetic Macular Edema Rajiv Raman and Muna Bhende

Sri Bhagwan Mahavir Introduction macular edema, often it is difficult to assess Vitreoretinal Services, Over the last one decade the management of dia- these features.10 Sankara Nethralaya betic macular edema has undergone a paradigm change.1 This is attributed to the newer diagnostic Fundus fluorescein angiography Correspondence to: tests and pharmacological agents. There are Rajiv Raman, enough good randomized controlled trials to prove • Desirable to have baseline FFA done in all Senior Consultant, the efficacy of these drugs. However, in clinical cases with DME. If otherwise contraindicated, Sri Bhagwan Mahavir practice, there are many situations where the at least a baseline fundus photo (ETDRS 7 Vitreoretinal Services, application of the findings of these clinical trials Field) should be done. Sankara Nethralaya. is often difficult. The aim of this article is to have Email: [email protected] • Preferably in cases where vision loss is dispro- a consensus statement on initial workup, diagno- portional to clinical picture (ischemic maculo- sis and management of diabetic macular edema. pathy), in cases where there is a suspicion of neovascularization, in cases of mixed retino- Initial assessment of diabetic pathy and those who are non-responders to macular edema treatment. History • Avoided in pregnancy, patients with history of • History regarding duration of diabetes, past serious adverse events during previous FFA glycemic control (hemoglobin A1c), and patients with allergy to fluorescein and Medications (especially insulin, oral hypogly- severely impaired renal function. cemics, antihypertensives, and lipid-lowering drugs), systemic history (e.g., renal disease, Systemic cardiovascular events, systemic hypertension, • Monitor fasting and post-prandial sugars, past serum lipid levels, pregnancy). glycemic control (hemoglobin A1c), Blood • History related to drugs causing macular pressure and lipid profile (preferable in patient edema (Thiazolidinediones, fingolimod (used in presenting with extensive exudates at macula) MS), tamoxifen, taxanes, niacin, interferons anemia and Renal function tests (Blood – and prostaglandin analogs).2 8 urea creatinine and microalbuminuria/ albuminuria).11,12 Ocular examination • Either access the patients recent records/ask • Detailed patient assessment should include a the patient to get these tests done and show to complete ophthalmic examination, including his treating physician/or order the investiga- visual acuity (preferably by a ETDRS/Log MAR tions and then appropriately refer to physician. chart) and the identification and grading of sever- ity of DR and presence of DME for each eye.9 Center-involving and non-center involving diabetic macular edema Assessment: clinically by Slit lamp biomicroscopy Investigations and by SD-OCT OCT • All patients with DME should undergo OCT Center involving DME (Both Raster and radial scans). Retinal thicken- Clinically: On clinical examination, definite ing (Central subfield and inner ETDRS ring retinal thickening due to diabetic macular edema thickness measurement), presence of involving the center of the macula. vitreomacular adhesion or traction and mor- On SD-OCT phological features like presence of neurosen- sory detachment, cystic spaces, foveal contour • Loss of foveal contour should be noted. • Cystic space involving center of fovea. • The features suggestive of prognosis-like hori- • Neurosensory detachment involving the center zontal and vertical extent of IS-OS disruption, of fovea ELM disruption and hyper reflective foci (HFs) within the neurosensory retina should be • Retinal thickening on SD OCT: central subfield noted. However, in presence of gross cystoid thickness on OCT >290 μm for women, >305

50 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Preferred Practice Pattern

μm in men on spectral domain OCT (Zeiss • Grid laser treatment of areas of thickened cirrus). Heidelberg spectralis: ≥305 μmin retina showing diffuse fluorescein leakage and/ women, and ≥320 μm in men.13 or capillary dropout. Must check the accuracy of OCT scan by ensur- ing it is centered and of adequate quality (for Situation 2: Non-center involving macular edema with Zeiss Stratus, standard deviation of center point few cystic spaces involving fovea (minimal center thickness should be ≤10% of the center point involvement)16 thickness and signal strength should be ≥6). • If the vision is compromised, intravitreal anti-VEGF can be the treatment of choice Non-center involving DME • If good vision (6/6), asymptomatic: laser Clinically: On clinical examination, definite according to the ETDRS guidelines retinal thickening due to diabetic macular edema within 3,000 μm of the center of the macula but • If symptomatic and vision is good (6/6): intra- not involving the center of the macula. vitreal anti-VEGF On SD-OCT Cystic spaces and/or retinal thickening in non- Situation 3: Center involving macular edema converting central macular subfields to non-center involving macular edema after intravitreal injections

Center and non-center involvement in CSME • During monthly follow-up after anti-VEGF CSME is a form of DME that was precisely defined treatment the visit in which the edema by the ETDRS as any of the following criteria becomes non-center involving, laser according being met14: to the ETDRS guidelines can be done. However, the follow-up visits after anti-VEGF μ 1 Any retinal thickening within 500 m of the injections should be continued as usual. center of the macula.

2 The presence of hard exudates at or within Situation 4: predominantly non-center involving 500 μm of the center of the macula, if asso- macular edema (ring of circinates) after intravitreal ciated with thickening of the adjacent retina injections or laser with plaque of hard exudate and (not residual hard exudates remaining after the normal foveal contour disappearance of retinal thickening) • Control of systemic status (serum lipids), refer- 3 A zone, or zones, of retinal thickening 1 disk ral to physician to initiate lipid lowering drugs. area or larger, any part of which is within 1 Intravitreal steroids (1st Choice) can be consid- disk diameter (1 disc = 1500 μm) of the center ered after assessing the risk (Glaucoma). Laser of the macula. may aggravate subfoveal deposits and should be avoided.17 Criterion 1: Center involving; Criterion 2 and 3: non-center involving Situation 5: treatment naïve center—involving macular edema Management of Diabetic macular edema Anti-VEGF therapy is the first line of treatment Situation 1: Non-center involving macular edema for all DME patients without traction but with Laser according to the ETDRS guidelines14,15: central involving macular edema. On monthly • Focal photocoagulation: treatment of individ- follow-up, look for Visual acuity and OCT for ual microaneurysms that fill with fluorescein improvement. and/or leak, as well as other points of leakage • OCT and/or vision shows improvement: con- such as intraretinal microvascular tinue the treatment with anti-VEGF abnormalities. • OCT shows progressive improvement but vision • Optional: treatment of microaneurysms (or not improving: continue anti-VEGF, but con- punctate hemorrhages) <125 μm in longest sider angiogram to look for ischemia at 3 diameter that did not fill with fluorescein; months. leaks within hemorrhages; treatment of micro- aneurysms or other focal points of leakage in • Vision improving but no OCT improvement: the retina further than 2 DD from the center of continue the treatment with anti-VEGF. Can the macula. consider adding laser, also look for VMA. • Avoid: treatment of nerve fiber layer retinal • No improvement on OCT and no visual gain: hemorrhage (flame or splinter hemorrhage) At 3 months, consider angiogram and then and blot hemorrhage >125 μm in size. plan rescue treatment. Either switch to other

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 51 Preferred Practice Pattern

anti-VEGF agent or consider steroid or con- previously. Evaluate the systemic factors for sider adding laser. recurrence. When to stop injections18: • ‘ ’ Success ; vision improved to 6/6 and on OCT, Situation 7: Proliferative diabetic retinopathy with return to normal foveal contour with reversal macular edema of thickening, disappearance of cystic spaces and NSD. • If no traction: complete Pan retinal photo- • ‘No further improvement’ Defined as <10% coagulation along with anti-VEGF and then decrease in central subfield thickness and <5 subsequent management of macular edema letter increase in visual acuity since the most according to the protocol. recent injection and, in the opinion of the treating ophthalmologist, it seems unlikely that • In presence of vitreous hemorrhage with hazy additional treatment would provide any further view of retina with suspected diabetic macular benefit. edema: PRP to the extent possible and Once injections are stopped, close monitor- pharmacological agents. ing (at least every 3 months) with either an • In the presence of extramacular traction: PRP ‘ ’ as-needed or a treat and extend treatment with burns 2 DD away from TRD, macular approach should be done. edema can be treated as usual protocol. Retreatment should be considered in any case that involves significant fluid reappear- • In the presence of traction threatening or ance. However, clinical judgment is required. involving fovea: vitrectomy is indicated. When to switch to other agents

Patients with progressive worsening of vision Situation 8: center involving macular edema with over three consecutive visits in the presence of vitreoretinal surface abnormalities active DME (i.e., when other causes of vision loss have been excluded) can be considered as • Evaluate the vitreoretinal interface on OCT. non-responders. • Focal vitreomacular traction with macular Situation 6: Previously treated center—involving edema: vitrectomy is the choice. macular edema with multiple Anti-VEGF injections/ • Extrafoveal traction site(s) without traction at Steroid injections/laser the vitreofoveal site: anti-VEGF treatment can • Stable: Control of systemic factors and be initiated, with a close watch at the extra- follow-up based on time of last injection. foveal traction site on follow-up. However, if the traction is significant, option of IVTA/ • Resistant: Evaluate with FFA and OCT. Ozurdex can be considered. ✓ Identify the ETDRS treatable lesions (retinal microaneurysms located between 500 and • Broad adherent epiretinal membrane with 3000 μm from the foveal center, retinal retinal thickening (VMA): in presence of microaneurysms located between 300 and 500 changes due to diabetic macular edema, cystic μm from the foveal center causing persistent spaces, NSD, retinal thickening, diffuse leak on CSME despite first laser treatment, areas of FFA: treat like center involving macular diffuse retinal leakage that could arise from edema. However, these show a relatively poor microaneurysms, dilated capillary bed or response to pharmacological treatment. intraretinal microvascular abnormalities and • Broad adherent epiretinal membrane with thickened ischemic zones) and treat if present. retinal thickening with no associated DME ✓ Carefully evaluate the follow-up protocols changes as mentioned above and thickening and response of previous treatments. Try to attributable to ERM: If asymptomatic; needs find out which treatment had the best observation with OCT on follow-up visits. response. Initiate the treatment with the same However, if symptomatic and shows worsening pharmacological agent and follow-up closely. on follow-up visits (drop in vision) can plan vitrectomy with epiretinal membrane removal. ✓ Evaluate the systemic control of Diabetes, If planning vitrectomy the prognostic features lipids, hypertension. Assess the renal status. which should be taken into account include Refer to a physician for adequate control. initial visual acuity (poorer VA has poor prog- • Recurrent: evaluate with FFA and OCT. Treat nosis), OCT features like IS-OS defects and according to center involvement. Treat with breaks in ELM, FFA features like the presence drug which had shown good response of ischemia, and status of optic nerve (pallor).

52 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Preferred Practice Pattern

Situation 9: Center involving macular edema in contributing to edema. Clinical and OCT pseudophakic eyes assessment of this is important.

• Differentiating pseudophakic from Diabetic macular edema in presence of DR: diffuse Situation 12: center involving macular edema in petalloid type of leakage with disc leakage on vitrectomized eyes the fluorescein angiogram and with very few • aneurysms and no hard exudates around the Pseudophakic eyes with center involving macula is suggestive of pseudophakic macular macular edema: intravitreal steroids should be fi 20 edema. considered as rst choice in suitable cases. • • Presence of diabetic macular edema with no In presence of recurrent vitreous hemorrhage component of Irvine Gass: treat as center with center involving macular edema: involving macular edema. However, if compli- anti-VEGF are the better choice. ance is an issue one can initiate the treatment • Selected cases where the risk of IOP spike and with intravitreal steroids. cataract is a concern: intravitreal anti-VEGF • Presence of both diabetic macular edema and can be considered. Close monitoring of IOP Irvine Gass: can plan treatment of diabetic and counseling of patient is important. macular edema along with non-steroidal anti- Consider choosing dexamethasone over IVTA inflammatory drugs. If no contraindications, to reduce IOP spikes. intravitreal steroids can be considered as an initial choice. Situation 13: ischemic macular edema • Time to start treatment of DR in fresh pseudo- • Access the ischemia with FFA and OCT phakia: if macular edema is detected after FFA: the minimum criterion for diagnosing cataract surgery, laser (macular) can be macular ischemia is moderate FAZ initiated after 1 month (after uncomplicated 21 irregularities. phacoemulsification); PRP if indicated can be ○ Moderate irregularities is defined as abnor- done early (with indirect laser delivery or mally dilated and tortuous capillaries budding gentle slit lamp delivery after sterilizing the into the FAZ, terminal arterioles/venules dir- contact lens) and intravitreal anti-VEGF can ectly abutting FAZ margins, and enlarged also be planned after 1 month. intercapillary spaces around the FAZ. The size is a minor criterion compared to the irregular- Situation 10: Macular edema during pregnancy19 ity of FAZ. Ischemia was diagnosed only when the longest diameter of FAZ was ž 1000 • Pregnancy may promote the onset of DR (in µ (the measurements should be made digitally about 10% of cases) as well as contribute to its using a FF 450plus fundus camera [VISUPAC worsening when already present. system, Carl Zeiss, Germany].

• The proliferative retinopathy must always be ○ Severe FAZ irregularity is defined as the treated; treatment should be earlier in pregnant destruction of the FAZ architecture: grossly women compared to non-pregnant women. enlarged FAZ with ‘pruned off’ arterioles.

• Pregnancy can also cause macular edema; it ○ Normal FAZ is defined as an FAZ <1000 µ spontaneously regresses during postpartum in the longest diameter, regular and round/ and therefore does not require immediate horizontally oval in shape. Mild undulations treatment. of FAZ were also considered normal. • However, if macular edema occurs early in the • Can also grade ischemia using ETDRS grading pregnancy and there is progressive deterior- system,22 from 0 (normal), to 1 (questionable), ation of vision, laser/intravitreal steroids 2 (less than half the original circumference should be preferred and anti-VEGF avoided. destroyed), 3 (more than half the contour destroyed but some remnants remain), and 4 (capillary outline completely destroyed). Situation 11: macular edema in young type I diabetes • Assessing ischemia on OCT: DME in presence • Management of DME in type 1 diabetes is of ischemia has retinal thickening in the outer similar to type 2; however, they need to be retinal layers. Inner retinal layers, including referred to their physician for optimal glycemic the ganglion cell layer (GCL) and RNFL, are control. thinned. • In cases of PDR with macular edema, there • In FFA grade 1 and 2: treat as non-ischemic is an increased risk of thickened PHF (Center and non-center involving)

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 53 Preferred Practice Pattern

• FFA Grade 3: avoid laser photocoagulation, • However, if the view is not good enough to can consider steroids in the presence of center treat DME, cataract surgery can be done either involving macular edema along with intravitreal anti-VEGFs, or 2 weeks after surgery and subsequent protocol • FFA Grade 4: would not benefit from any continued. treatment. • If the view is clear and treatment initiated, but even after three to four injections, the edema Situation 14: center involving macular edema with has not resolved; and during this time cataract history of recent stroke has worsened: cataract surgery can be planned • If a patient had stroke (cerebrovascular acci- and treatment of DME continued thereafter. dents) or myocardial infarction, within last 3 Can consider concurrent intravitreal injection months, do not initiate treatment with or injection post-surgery based on logistics. anti-VEGF. Treatment with laser or steroids • If during treatment of DME, patient also devel- can be considered in these patients. ops PCO, NdYAG capsulotomy can be planned • If the history is >3 months old, the treatment and treatment of DME can be continued as can be initiated with anti-VEGF. However, if usual. systemic risks of thromboembolic phenomenon fi are signi cant, it is best to consult a physician Situation 18: diabetic macular edema with optic nerve fi rst. abnormalities Differentiating NA-AION, papillopathy and Situation 15: diabetic macular edema in papillophlebitis: glaucomatous eyes • NA-AION: the optic disc edema in NAION may • In eyes with established glaucoma/glaucoma be diffuse or segmental, hyperemic or pale, but suspect/ocular hypertension: avoid intravitreal pallor occurs less frequently than it does in steroids. Even if intravitreal anti-VEGFs are AAION. A focal region of more severe swelling used, monitoring of IOP and if required aug- often is seen and typically displays an altitud- mentation of anti-glaucoma medications is inal distribution, but it does not correlate con- fi required. sistently with the sector of visual eld loss. Diffuse or focal telangiectasia of the edema- • For rescue treatment in this group, laser photo- tous disc may be present, occasionally promin- coagulation is preferred. ent enough to resemble a vascular mass or neovascularization. Situation 16: considering diabetic macular edema for • Papillopathy: acute onset of unilateral or bilat- vitrectomy eral disc edema in usually in young, type 1 • Focal vitreomacular traction: vitrectomy is the diabetics, sometimes even type 2 diabetes, fi choice. without the usual defects in visual eld and pupillary function associated with NAION or • Broad vitreoretinal adhesion: if anti-VEGFs optic neuritis. and rescue treatment have failed to resolve the • macular edema and the ophthalmologist feels Papillophlebitis: typically shows more prom- that there is a scope of improvement, vitrec- inent retinal venous congestion, peripheral tomy can be considered. retinal hemorrhages. • • Diffuse diabetic macular edema: if does not In AION cases, FFA shows early disc hypo- fl show desired outcome after primary and recue uorescence due to hypoperfusion with late treatment, can be considered for vitrectomy leakage around the affected segment. However, with or without ILM peeling. Patients vision, in diabetic papillopathy cases the FFA shows a optic disc status, and macular perfusion need very early disc leakage that increases through- fl to be evaluated first. out the study. The early hyper uorescence is most likely due to telangiectasia of the optic disc. Fields typically show altitudinal defect in Situation 17: Cataract with Diabetic macular edema NA-AION which are not seen in papillopathy. • Diabetic macular edema with cataract: as long NA-AION with macular edema: differentiate as there is a clear enough view to see DME whether the macular edema is due to Macular star clinically and on OCT treat DME according to seen in NA-AION or diabetic macular edema. FFA the protocol. Once macular edema is treated, plays an important role. Identify the presence of one can plan cataract surgery. Ideally we can DR lesions which can cause edema (MA, diffuse wait for 3 months after cataract surgery. leak, IRMA). If it is due to diabetic macular

54 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Preferred Practice Pattern edema, treat as either center involving or non- intravitreal injections should be avoided. Look for center involving. If it is due to NA-AION, treat- non-invasive alternatives such as laser if feasible. ment of NA-AION would resolve the edema, no Fluctuating glycemic control: These patients treatment by intravitreal injections is required. pose a challenge for the treating physician, as Papillopathy with diabetic macular edema: before each anti-VEGF injection, the blood sugar treat the macular edema as any other diabetic has to be <200 mg%; fluctuating glycemic control macular edema. can alter the compliance of regular intravitreal Papillophlebitis with macular edema: FFA to injections. determine whether the macular edema is due to Monthly follow-up: As diabetics, often also diabetes or vein occlusion. If due to diabetes, treat have other co-morbid conditions which require as any other diabetic macular edema. In these regular care like nephropathy, cardiovascular pro- cases, one should rule out inflammatory causes blems, neuropathy etc.; regular monthly follow-up as well. may not be feasible in some of them. If compli- ance is an issue, laser treatment can be considered. Situation 19: diabetic macular edema with anemia • In the majority of patients, the anemia is Conclusion related to renal dysfunction and may require Management of diabetic macular edema is a chal- subcutaneous erythropoietin injections for lenging situation; as in clinical practice we come treatment. The macular edema usually across many combinations of phenotypes and improves with it; however, one should keep a clinical scenario. The choice and protocols of close watch on proliferative component, as management may slightly differ; however, princi- erythropoietin can worsen the same. ples of treatment remain same. The clinical trials in the last decade with pharmacotherapy have • Anti-VEGF can be the preferred agent in pres- largely helped in changing paradigms in manage- ence of anemia and center involving DME. ment of DME.

Situation 20: diabetic macular edema with mixed References retinopathy 1. Arevalo JF. Diabetic macular edema: changing treatment paradigms. Curr Opin Ophthalmol. 2014;25(6):502–7. • The management of diabetic macular edema 2. Idris I, Warren G, Donnelly R. Association between remains unchanged; however, the history of thiazolidinedione treatment and risk of macular edema among cardiovascular risk factors should be sought patients with type 2 diabetes. Arch Intern Med. 2012;172 – and if required a physician consultation should (13):1005 11. 3. Nieraj J, Tariq Bhatti M. Fingolimod-associated macular edema. be done. Neurology. 2012;78(9):672–80. • In cases of accelerated hypertension, anti- 4. Nayfield SG, Gorin MB. Tamoxifen-associated eye disease. A 14 – VEGF should be avoided. review. J Clin Oncol. 1996; (3):1018 26. 5. Modi D, Dubovy SR. Non-leaking cystoid maculopathy secondary to systemic paclitaxel. Ophthalmic Surg Lasers Situation 21: Diabetic macular edema with lattice Imaging Retina. 2013;44(2):183–6. Trechot P, degenerations 6. Conart JB, Trechot F, Petitpain N, Angioi K, A careful examination of the periphery, and Berrod JP. Pathophysiological hypothesis regarding the role of nicotinamide in the genesis of niacin-induced macular edema. J prophylactic treatment of any lesions that could Fr Ophtalmol. 2014;37(4):e49–51. predispose to RD, is preferable. The gap between 7. Sheth HG, Michaelides M, Siriwardena D. Cystoid macular laser prophylaxis and the injection should ideally edema and visual loss as sequelae to interferon alpha treatment be 3 weeks. of systemic hepatitis C. Indian J Ophthalmol. 2010;58(2):147–8. 8. Brasil OF, Brasil MV, Ventura MP, Maia HS. Bilateral and simultaneous cystoid macular edema associated with latanoprost Challenges in any intravitreal injection among use: report of two cases. Arq Bras Oftalmol. 2010;73(2):186–8. Beck RW, diabetics 9. Moke PS, Turpin AH, Ferris FL III, SanGiovanni JP, Need for bilateral injection: On many occasions Johnson CA, Birch EE, Chandler DL, Cox TA, Blair RC, Kraker RT. A computerized method of visual acuity testing: there is a requirement of multiple Anti-VEGF adaptation of the early treatment of diabetic retinopathy study injections in both eyes. Ideally a gap of a week or testing protocol. Am J Ophthalmol. 2003;135:194–205. at least 3 days should be kept between both the 10. Bolz M, Schmidt-Erfurth U, Deak G, Mylonas G, Kriechbaum K, eyes. Scholda C; Diabetic Retinopathy Research Group Vienna. Patient with non-healing foot ulcer: This poses Optical coherence tomographic hyperreflective foci: a a risk of infection. Before injections make it sure morphologic sign of lipid extravasation in diabetic macular edema. Ophthalmology. 2009;116(5):914–20. the patient is in care of a surgeon/physician. The 11. Wan Nazaimoon WM, Letchuman R, Noraini N, Ropilah AR, attendant and patient should be counseled to do Zainal M, Ismail IS, Wan Mohamad WB, Faridah I, foot dressing before doing ocular dressing or Singaraveloo M, Sheriff IH, Khalid BA. Systolic hypertension instilling the drops. In presence of active infection, and duration of diabetes mellitus are important determinants of

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 55 Preferred Practice Pattern

retinopathy and microalbuminuria in young diabetics. Diabetes 17. Cekiç O, Bardak Y, Tig˘ US, Yildizog˘ lu U, Bardak H. Quantitative Res Clin Pract. 1999;46:213–21. evaluation of reduction of plaque-like hard exudates in diabetic 12. Gaede P, Vedel P, Parving HH, Pedersen O. Intensified macular edema after intravitreal triamcinolone injection. Int multifactorial intervention in patients with type 2 diabetes Ophthalmol. 2008;28(2):95–9. mellitus and microalbuminuria: the Steno type 2 randomised 18. Aiello LP, Beck RW, Bressler NM, Browning DJ, Chalam KV, study. Lancet. 1999;353:617–22. Davis M, Ferris FL III, Glassman AR, Maturi RK, Stockdale CR, 13. Bressler NM, Edwards AR, Antoszyk AN, Beck RW, Topping TM. Rationale for the diabetic retinopathy clinical Browning DJ, Ciardella AP, Danis RP, Elman MJ, Friedman SM, research network treatment protocol for center-involved diabetic Glassman AR, Gross JG, Li HK, Murtha TJ, Stone TW, Sun JK, macular edema. Ophthalmology. 2011;118(12):e5–14. doi:10. Diabetic Retinopathy Clinical Research Network. Retinal 1016/j.ophtha.2011.09.058. thickness on Stratus optical coherence tomography in people 19. Sinclair SH, Nesler C, Foxman B, Nichols CW, Gabbe S. with diabetes and minimal or no diabetic retinopathy. Am J Macular edema and pregnancy in insulin-dependent diabetes. Ophthalmol. 2008;145:894–901. Am J Ophthalmol. 1984;97(2):154–67. 14. Early Treatment Diabetic Retinopathy Study Research Group. 20. Yanyali A, Aytug B, Horozoglu F, Nohutcu AF. Bevacizumab Photocoagulation for diabetic macular edema. Early Treatment (Avastin) for diabetic macular edema in previously vitrectomized Diabetic Retinopathy Study report number 1. Arch Ophthalmol. eyes. Am J Ophthalmol. 2007;144(1):124–6. 1985;103:1796–806. 21. Shukla D1, Kolluru CM, Singh J, John RK, Soman M, Gandhi B, 15. Early Treatment Diabetic Retinopathy Study design and baseline Kim R, Perumalsamy N. Macular ischaemia as a marker for patient characteristics. ETDRS Report Number 7. Ophthalmology nephropathy in diabetic retinopathy. Indian J Ophthalmol. 1991;98:741–56. 2004;52(3):205–10. 16. Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, 22. Sim DA1, Keane PA, Fung S, Karampelas M, Sadda SR, Edwards AR, Ferris FL III, Friedman SM, Glassman AR, Fruttiger M, Patel PJ, Tufail A, Egan CA. Quantitative Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial analysis of diabetic macular ischemia using optical evaluating ranibizumab plus prompt or deferred laser or coherence tomography. Invest Ophthalmol Vis Sci. 2014; triamcinolone plus prompt laser for diabetic macular edema. 55(1):417–23. Ophthalmology. 2010;117:1064–77 e35.

How to cite this article Raman R, Bhende M. Diabetic Macular Edema, Sci J Med & Vis Res Foun 2015;XXXIII:50–56.

56 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Review article

Micro Incision Vitrectomy Surgery (MIVS): An Overview Pramod S. Bhende and Aneesha Lobo

Sri Bhagwan Mahavir Introduction In comparison to 20 gauge, the MIVS cutter Vitreoretinal Services, In today’s world of nano-technology where bigger port is smaller and closer to the tip (Fig. 1). A Sankara Nethralaya no longer means better, everything from smart- smaller port and a proximity closer to the tip phones to surgical incisions are getting smaller maybe advantageous when performing complex Correspondence to: and more refined. The advantages of smaller sur- manoeuvres, such as shaving of the vitreous base, Pramod S Bhende, gical incision have resulted in faster postoperative working near detached mobile retina, membrane Deputy Director and Senior recovery. segmentation or delamination. The MIVS system Consultant, Vitreoretinal surgery is no exception. We have also comes equipped with higher cutting rates Sri Bhagwan Mahavir come a long way since the time of open sky extending up to 5000–8000 cpm; which reduces Vitreoretinal Services, vitrectomy and Machemer’s first 17-gauge closed the likelihood of uncut vitreous fibers going Sankara Nethralaya. 1 E-mail: [email protected] pars plana vitrectomy (PPV) in 1971. In 1974, through the cutter port, thereby reducing dynamic O’Malley and Heintz2 introduced a smaller vitreoretinal traction with less chance of iatro- 20-gauge (G) vitrector (0.9 mm diameter) for use genic retinal tears and damage to the retinal with the three-port sclerotomy system that became surface. To achieve this high cutting rate without the gold standard for modern PPV and has been vibrations for better stability and precision cutting the standard of care for almost three decades. newer cutters do not have spring to drive the However, in current times, just attaching the guillotine. retina is not enough. Variables like patient comfort (both intra and post-operative), surgical Rigidity time and precision, post-operative recovery time, The main concern while using the smaller gauge surgically induced refractive error, cosmesis, etc. instruments is the bending or breakage of the are becoming increasingly important. To take flexible instruments and difficulty in manoeuvring these factors into account, ‘Transconjunctival the globe with the help of these flimsy instru- sutureless vitrectomy’ (TSV), subsequently ments. This problem is more noticeable with the renamed and popularly known as microincision 25- and 27-gauge instruments as compared to 23 vitrectomy system (MIVS) has come about. The gauge. In order to overcome this, second gener- 25-gauge vitrectomy was introduced3 in 2002 by ation instruments, 25+ and 27+, respectively, have Fujii et al followed by the 23 gauge in 2005 by been introduced by adding 5 mm supporting Eckardt4 and Stanley Chang which combined sleeve near proximal end to make instruments the benefits of 20 and 25 gauge. In 2010, stiffer and less malleable. However, this reduces Oshima introduced even smaller, 27-gauge the effective working length of the instrument instrumentation.5 which is disadvantageous while operating on eyes As a result of these advances, vitreoretinal sur- with longer axial lengths. Careful positioning of geons now have multiple choices when determin- the sclerotomies can also reduce tool flexion. ing their operative approach. In this article, we would like to give a brief overview of the various Illumination MIVS systems available. Reducing the diameter of a light pipe by 20% theoretically reduces the amount of illumination Instrumentation by ∼35%. The conventional illumination (halogen) In MIVS, three micro-cannulas are inserted in the used in 20-gauge PPV is not adequate for MIVS. pars plana (with the help of insertion trocar) Currently, with the new-generation xenon and through the conjunctiva and sclera through a mercury vapor illumination sources, illumination two-step incision. The infusion line and vitreoret- inside the vitreous cavity has greatly improved. inal instruments are then introduced into the vit- When combined with chandelier illuminators or reous cavity through these cannulas. At the end of multifunction instruments, these sources have the procedure, the cannulas are removed without made bimanual microincisionvitrectomy a reality. suturing either the sclera or the conjunctiva. The inner diameters of the 25- and 23-gauge Aspiration and flow rates cannulas are 0.57 and 0.65 mm, respectively,3,4 in In accordance to the Poiseuille’s law, which states contrast to the 0.9 mm diameter of a conventional that the flow through a tube is proportional to the 20-gauge incision while that of the 27-gauge fourth power of the radius of the tube, it is cannula is 0.4 mm.5 These narrow incisions do not evident that even a minor reduction in the inner need to be sutured, thus providing minimal surgi- diameter of the tubing will result in a significant cal trauma and brief recovery times. reduction in the flow across the tube. As a result

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 57 Review article

Fig. 1. 23G cutter port is closer to tip compared to 20G cutter

Fig. 2. Dual actuation lines (ALCON) allows duty cycle control, to make cutting more effective

Fig. 3. Comparison between B&L and Alcon 25 gauge probe

58 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Review article of different flow characteristics imparted by a Previous vitrectomy contributed to wound reduction in the size of the opening of small- leakage in 23-gauge vitrectomy in a study con- gauge vitreous cutters, higher infusion and aspir- ducted by Woo et al.7 Previous sclerotomy sites ation rates are necessary to optimize flow and vit- are structurally weaker because of scarring and reous removal. Higher aspiration flow rates will fibrosis and reduced rigidity of the sclera could reduce the surgical time but at the cost of risking increase the likelihood of wound leakage. A clin- inadvertent breaks and retinal engagement in the ical study8 using 25-gauge MIVS did correlate cutter port, especially when working in the periph- younger age as a contributing factor for early ery or with detached retina. ‘Aspiration flow limit’ postoperative hypotony. Gupta et al.9 found post- is a feature complimentary to variable duty cycle operative day 1 intraocular pressure to be statistic- and high cut rate in newer machines and once set, ally lower than preoperative pressures, when eyes it maintains continuous state of fluidic stability in were left fluid filled. This was not the case in air theeye,preventingsuddendecreaseinintraocular or gas filled eyes. pressure and pulsatile traction on the retina. Post-operative endophthalmitis Complications Kaiser et al. in their presentation at the 2007 Vail Wound leakage Vitrectomy meeting reported 0.23% incidence of Post-operative wound leak has always been a endophthalmitis in 3103 consecutive eyes under- concern with MIVS.6 These issues can be going MIVS. This is in contrast to only one case addressed by proper wound construction. of endophthalmitis in 5498 consecutive 20-gauge Displacement of the conjunctiva before entry so vitrectomies (an incidence of 0.0018%) performed that the conjunctival and scleral incisions are mis- by the same surgeons, at the same institution, aligned has found to reduce wound leakage. over the same period.10 However, four other Oblique/angled entry has less incidence of wound studies (three with level II evidence) that compared leakage as compared to perpendicular entry and rates of acute endophthalmitis between 20- and biplanar incisions are advantageous over uni- 25-gauge vitrectomy did not show(11–14) a statis- planar ones. tically significant difference in incidence of endophthalmitis. In a similar comparative study of 23-gauge and 20-gauge cases, no case of endophthalmitis was observed among 943 eyes after 23-gauge PPV.15

Indications of MIVS 23 Gauge Though it can be used universally, 23-gauge system is ideally suited for rhegmatogenous retinal detachment surgery and for diabetic vitrectomies. It can also be used in cases of endophthalmitis and trauma especially foreign body removal.

25 and 27 Gauge They are more suitable for macular surgery (Macular hole/macular pucker/epiretinal mem- Fig. 4. Four-port vitrectomy for ROP using MIVS brane) and simple cases of vitreous hemorrhage.

Fig. 5. Alcon 27 gauge vitrectomy system

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 59 Review article

Branch vein decompression (sheathotomy) can vitreoretinal diseases. Each system has its advan- also be performed. 25G instruments are also pre- tages and disadvantages. The optimum gauge and ferred in pediatric cases. settings have to be selected after careful deliber- ation to provide the best possible surgical Advantages of MIVS over conventional 20 gauge outcome. • Sutureless procedure: so better patient comfort. • Less inflammation: faster healing and recovery of visual acuity. References 1. Machemer R, Parel JM, Norton EW. Vitrectomy: a pars plana • Less surgery induced refractive error. approach. Technical improvements and further results. Trans 76 – • Am Acad Ophthalmol Otolaryngol. 1972; :462 6. Reduced conjunctival scarring: Useful for 2. O’Malley C, HeintzRM Sr. Vitrectomy with an patients requiring multiple surgeries and also alternative instrument system. Ann Ophthalmol. 1975;7:585–88; prior to or anticipated glaucoma filtering sur- 91–94. geries or candidates with ocular surface 3. Fujii GY, De Juan E Jr, Humayun MS, et al A new 25-gauge disorders. instrument system for transconjunctival sutureless vitrectomy surgery. Ophthalmology. 2002;109:1807–12; discussion 13. • Port design helps in more complete vitrectomy 4. Eckardt C. Transconjunctival sutureless 23-gauge vitrectomy. and easier dissection of proliferative Retina. 2005;25:208–11. membranes. 5. Oshima Y, Wakabayashi T, Sato T, et al A 27-gauge instrument system for transconjunctival sutureless microincisionvitrectomy • Higher cut rates and smaller port aperture surgery. Ophthalmology. 2010;117:93–102. reduces the chances of inadvertent retinal 6. Lakhanpal RR, Humayun MS, Juan E Jr, et al Outcomes of breaks. 140 consecutive cases of 25-gauge transconjunctival surgery for posterior segment disease. Ophthalmology. 2005;112:817–24. Disadvantages of MIVS when compared to 20 gauge 7. Woo SJ, Park KH, Hwang J, Kim JH, Yu YS, Chung H. Risk factors associated with sclerotomy leakage and postoperative • Actual time for performing vitrectomy may be hypotony after 23-gauge transconjunctival sutureless longer vitrectomy. Retina. 2009;29:456–63. 8. Byeon SH, Lew YJ, Kim M, Kwon OW. Wound leakage and • Not suitable for cases where extensive dissec- hypotony after 25-gauge sutureless vitrectomy: factors affecting tion is needed and in eyes where fragmatome postoperative intraocular pressure. Ophthalmic Surg Lasers have to be used Imaging. 2008;39:94–9. 9. Gupta OP, Weichel ED, Regillo CD, et al Postoperative • Higher infusion pressure may cause optic nerve complications associated with 25-gauge pars planavitrectomy. damage Ophthalmic Surg Lasers Imaging. 2007;38:270–5. 10. Hilel Lewis. Sutureless microincision vitrectomy surgery: • fl Smaller incision may limit the maximum ow unclear benefit, uncertain safety (Editorial). Am J Ophthalmol. across the port 2007;Oct:613–15. Hu AY, • 11. Bourges JL, Shah SP, et al Endophthalmitis after pars Flimsy instruments which may deform or planavitrectomy: a 20- and 25-gauge comparison. break during surgery Ophthalmology. 2009;116:1360–65. 12. Mason JO III, Yunker JJ, Vail RS, et al Incidence of • With long trocar blade, there is an increased endophthalmitis following 20-gauge and 25-gauge vitrectomy. risk of retinal injury in eyes with anteriorly Retina. 2008;28:1352–54. displaced retina 13. Shimada H, Nakashizuka H, Hattori T, et al Incidence of • endophthalmitis after 20- and 25-gauge vitrectomy: causes and Increased risk of post-operative hypotony, prevention. Ophthalmology. 2008;115:2215–20. choroidal detachments and endophthalmitis 14. Chen JK, Khurana RN, Nguyen QD, Do DV. The incidence of due to gaping wounds endophthalmitis following transconjunctival sutureless 25- vs 20-gauge vitrectomy. Eye. 2009;23:780–4. Parolini B, Conclusion 15. Romanelli F, Prigione G, Pertile G. Incidence of endophthalmitis in a large series of 23-gauge and 20-gauge The development of MIVS has provided surgeons transconjunctival pars planavitrectomy. Graefes Arch Clin Exp with new options in the surgical treatment of Ophthalmol. 2009;247:895–8.

How to cite this article Bhende P.S., Lobo A. Micro Incision Vitrectomy Surgery (MIVS): An Overview, Sci J Med & Vis Res Foun 2015;XXXIII:57–60.

The authors have no commercial associations that may pose a conflict of interests in connection with this article.

60 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Preferred practice pattern

Endophthalmitis: Current Trends, Drugs and Protocols

Aditya Verma, Vinata Muralidharan and Eesh Nigam

Shri Bhagwan Mahavir A brief summary of management of endophthal- injections); trauma; endogenous; contiguous Vitreoretinal Services, mitis is being highlighted with pertinent informa- spread (corneal ulcer, scleral abscess) Sankara Nethralaya tion regarding the relevant and most commonly b Onset: acute, sub-acute or chronic used antibiotics. Endophthalmitis, in any clinical Correspondence to presentation, should be considered as an ophthal- c Progression: rapid or gradual Aditya Verma, mic emergency. Tailored approach to each individ- Consultant, d Symptoms: decreased vision, pain, redness, ual patient is warranted. fl Shri Bhagwan Mahavir oaters, lacrimation, photophobia Definition: Inflammation of intraocular fluids and Vitreoretinal Services, e Systemic illness: uncontrolled diabetes, chronic Sankara Nethralaya. tissues (Fig. 1), which can be either infectious or debilitating illness, endocarditis, liver abscess, Email: [email protected] sterile. long-term hospitalization Classification (based on etiology):1

a Exogenous (post-operative [most common], Nuggets traumatic, local spread). The work up of a patient with endophthalmitis b Endogenous (metastatic): hematogenous spread. should be considered as utmost emergency, since the highly virulent organisms and their toxins can c Non-infectious (sterile uveitis, lens induced/ damage the ocular structures within hours. phaco-anaphylactic, sympathetic ophthalmia).

Nuggets 1. The most common etiology of endophthalmitis is post-operative (cataract 2. Work up extraction and bleb related endophthalmitis).2 2. The acute and fulminant presentations of a Initial ophthalmic assessment endophthalmitis should be differentiated from i Initial visual acuity (unaided and with cor- Toxic Anterior Segment Syndrome (TASS). rection, both eyes) ii Examination of the lids and adnexa Work sheet of a case of infective iii Examination of specific areas of interest endophthalmitis (filtering bleb, trauma site, cataract wound) At presentation iv Anterior segment examination (with 1. History taking (Table 1) detailed documentation) v Intra-ocular pressure (digital/applanation a Inciting event: surgery (cataract/glaucoma/ depending upon corneal clarity and vitreoretina/keratoprosthesis/intravitreal integrity)

Figure 1. Clinical picture of (a) post-operative endophthalmitis and (b) filtering bleb-related endophthalmitis.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 61 Preferred practice pattern

Table 1: Classification of post-operative endophthalmitis1,2 Features Time Commonly Commonly Presence of implicated associated of hypopyon Type presentation organisms surgical procedure and pain

Fulminant <4 days Gram negative bacteria, Cataract surgery Very common Pseudomonas aeruginosa, Streptococcus pneumonia, Staphylococcus aureus Acute 2–11 days Coagulase-negative Cataract surgery Very common (average 5–7 staphylococci, Staphylococcus With posterior days) aureus, streptococcus species, capsule rupture, Gram-negative bacteria vitreous loss Secondary IOL implantation Sub-acute/ 2 weeks– Propionibacterium acnes, Cataract surgery Uncommon delayed months Staphylococcus epidermidis, With thickened, onset (average 4–6 fungi (Candida parapsilosis), cheesy posterior Most common weeks) Corynebacterium sp. capsular presentation is vision thickening loss Chronic/late Months–years *Streptococcus sp., Filtering bleb Very common onset (Average >6 Enterococci, Hemophilus surgery ‘White on red weeks) influenza, Staphylococcus With anti-fibrotic appearance’ (white species agents, thin bleb surrounded by walled, cystic congested leaking blebs conjunctiva3) **Fungi Cataract surgery Uncommon *Acute onset presentation. **Chronic, late onset presentation.

vi Extra-ocular movements Nuggets fi vii Detailed fundus evaluation after dilatation The most relevant ultrasound ndings to be looked for are: amount of exudation, retinal status, with good documentation choroidal thickness, axial length, and the presence viii Ultrasound B scan if hazy media of T sign, retained intra-ocular foreign body or lens matter. ix Written informed consent for further management x Immediate microbiology requisition, informing anesthetist/OR staff (if pediatric/ 3. Procedure of anterior chamber tap fulminant) (AC tap) xi Anterior chamber tap (for initial microbio- a. Requirements (Fig. 2) logical evaluation) i Microbiology personnel/inoculation media (if xii Empirical therapy (systemic, intravitreal, done after working hours) topical in combinations) ii Sterile transport tube with a rubber bunk xiii Admit and close watch (initially over inside hours) iii 1 ml sterile (tuberculin) syringe b Check previous medical records and relevant iv 30G sterile needle (27G for thick exudates) systemic history, inform the patient and rela- tives about the seriousness of the condition v Lid speculum c Inform the concerned medical staff (surgeon, vi Sterile cotton tip applicators nursing staff, operation theatre) vii Protective hand gloves d Inform the primary surgeon (in case of viii Lighting source (indirect ophthalmoscope in-house infection) (preferred)/slit lamp)

62 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Preferred practice pattern

Figure 2. Instruments required for anterior chamber/vitreous tap and intravitreal injections.

Figure 3. The sterile test tube container used to transfer the sample (aqueous/vitreous/others) to microbiology laboratory. ix Proparacaine, povidone iodine eye drops vii Plan the site of tap based on AC depth, visi- bility, ease of access and the area of x Eye patch maximum exudation. b. Procedure viii With patient in primary gaze, introduce 30G/27G needle through the selected site on i Make the patient comfortable, explain the the limbus tangentially in a lamellar fashion, procedure in detail. keeping direction oblique over the iris surface (prevent direction towards lens) with active ii Check the written and informed consent suction. (adult/minor). ix Aspirate as much aqueous and exudates/ iii Wash hands thoroughly and air dry hypopyon as possible (without collapsing the (preferred). AC) (approximately 0.1–0.2 ml). iv Wear gloves, clean the periocular area with x Apply cotton tip applicator and withdraw the povidone iodine scrubs. needle. v Proparacaine eye drops (avoid lignocaine, as xi The syringe can be sent in a sterile this is bacteriostatic). transport tube to the microbiology lab vi Apply lid speculum. (Fig. 3).

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 63 Preferred practice pattern

xii Administer the intravitreal antibiotics (as per Drugs and treatment protocols (Table 2) the initial smear report/empirical if a delay is Nuggets expected in reporting) and patch with topical Primary objectives of endophthalmitis povidone iodine. management are eradication and control of xiii The patch should be removed after half an infection, management of complications and restoration of vision, in that order. hour and topicals started.

Nuggets 4. Intravitreal antibiotics 1. The aqueous should be collected with needle a. Requirements directed towards the exudates/hypopyon to i Basic requirements as in point 3a. enhance the possibility of microbial isolation and identification. ii Antibiotic vials (to be administered). 2. In an unco-operative or apprehensive patient, the fellow eye may be temporarily closed to iii Diluents (distilled/sterile water). minimize the anxiety caused by the visibility of iv Adjuvant (steroids dexamethasone). needle/syringe. v 5 or 10 ml sterile syringe.

Table 2 Outlines of management of endophthalmitis based on etiology (tailored approach warranted).7,8 Type Most common Initial systemic Initial intravitreal Need for Need for IOL pathogens treatment antibiotic vitrectomy removal (absolute indication)

Acute Coagulase negative I/V** or oral V+C+D* Yes, early if May be post-cataract Staphylococci (70%), third-generation severe surgery other Gram-positive cephalosporin/ cases/ (25%), Gram-negative fluoro-quinolones fulminant or (fulminant) fungal infection Sub-acute Propionibacterium No V (capsular bag) May be Yes cataract acnes and D needed surgery (Intravitreal) Post Coagulase-negative Fluoro-quinolones or V+C+D* Rarely (if it No intravitreal Staphylococci, viridians equivalent is severe) injection Streptococci Filtering bleb Streptococci, I/V** or oral 3rd V+C+D* Most cases, No related Hemophilus influenae generation early in cephalosporin/ fulminant fluoro-quinolones cases Post traumatic Bacillus cereus, I/V** Vancomycin V+C+D* Most cases, Varies (always Coagulase negative and either (Amphotericin/ early in with fungal Staphylococci, Fungi third-generation Voriconazole with fulminant etiology) (vegetative matter) cephalosporins/ no steroids (if cases fluoro-quinolones fungal)) Endogenous Staphylococcus aureus, I/V** or oral broad V+C+D* (or Mostly No bacterial Streptococci, spectrum antibiotics amikacin) needed Gram-negative bacilli (e. tailored to systemic g. Klebsiella) infection Endogenous Aspergillus, Fusarium Oral voriconazole Voriconazole or Yes Yes fungal (I/V** if fulminant) amphotericin (mould) Endogenous Candida species Oral voriconazole Voriconazole or Yes if vitritis Yes candida amphotericin Chronic post Aspergillus species, Oral voriconazole; Voriconazole or Yes Yes operative Candida species, rarely I/V** amphotericin B fungal Curvularia lunata voriconazole or Amphotericin B (highly toxic), or oral fluconazole *V, vancomycin; C, ceftazidime/cephazoline, D, dexamethasone. (Most commonly used initial empirical drugs based on clinical presentation.) **I/V, intravenous

64 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Preferred practice pattern

Table 3 Intravitreal drugs, doses and preparation techniques of most commonly used antibiotics.9,10 S. Name of Intravitreal Salient steps for preparation Remarks Frequency of no. antibiotic dose (1 ml tuberculin syringe) (if any) repeat (available (per 0.1 ml) injections** dose)

1 Vancomycin 1 mg 1. Add 5 ml distilled water Do not mix with 72 hours (500 mg) 2. Mix well (shake)—100 mg/ml other drugs, as it 3. Take 0.1 ml of drug solution gets precipitated 4. Dilute with 0.9 ml of sterile water (single dilution) 5. Mix well (moving air bubble up and down) 6. Discard 0.9 ml 7. Use 0.1 ml for injection 2 Ceftazidime 2.25 mg 1. Add 4 ml of distilled water Can be mixed 48–72 hours (1000 mg) (250 mg/ml) with steroid 2. Follow Steps 2–7asinrow2 preparation in the Use dexamethasone in Step 4 if same syringe indicated (single dilution) 3 Amikacin 125 µg 1. Take 0.1 ml solution (12.5 mg/ Can be mixed 24–48 hours (250 mg/2 ml) (previously 0.1 ml) with steroid recommended 2. Follow steps 4–6asinrow2 preparation in the 400 µg was 3. Take 0.1 ml solution same syringe highly retinal 4. Take 0.9 ml of distilled water (Double dilution) toxic) again and mix well Can be mixed with dexamethasone for final concentration (step 4) 4 Gentamycin 80 µg 1. Take 0.2 ml of Gentamycin (8 mg/ Extreme retinal 72–96 hours (80 mg/2 ml) 0.2 ml) toxicity, rarely 2. Dilute with 0.8 ml of distilled used now (double water dilution) 3. Mix well 4. Discard 0.9 ml of solution 5. Dilute with 0.9 ml of distilled water and mix well 6. Discard 0.9 ml of solution 7. Use 0.1 ml for injection 5 Amphotericin 5 µg 1. Add 10 ml of distilled water and Phototoxic, ?? 48 hours B (50 mg) mix well (5 mg/ml) dispensed in a 2. Follow steps 2–6asinrow2 brown (double 5. Again take 0.1 ml of solution and dilution) add 0.9 ml distilled water and mix well 6. Discard 0.9 ml of solution 7. Use 0.1 ml for injection 6 Voriconazole 50–100 µg 1. Add 19 ml of distilled water and (One and a half 48 hours (200 mg) mix well (10 mg/ml) dilution) 2. Take 0.1 ml solution and add 0.9 ml distilled water and mix well 2. Discard 0.5 ml of solution 5. Take 0.5 ml of sterile water and mix well (air bubble) 6. Discard 0.9 ml of solution 7. Use 0.1 ml for injection 7 Ciprofloxacin 100 µg Directly loaded from the sterile vial Not to be loaded 12 hours (200 mg/ and injected intraviteally, 0.05 ml from the topical 100 ml) preparation; since half-life is approx. 6 hours, daily injections are needed 8 Moxifloxacin 200 µg Take 0.05 ml of 0.5% moxifloxacin Directly taken 12 hours (preservative free) from topical preparations under sterile conditions 9 Imipenem 50–100 µg 1. Dilute with 100 ml of distilled Data not (250 mg) water available 2. Take 0.2 ml (0.5 mg) Continued

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 65 Preferred practice pattern

Table 3 Continued S. Name of Intravitreal Salient steps for preparation Remarks Frequency of no. antibiotic dose (1 ml tuberculin syringe) (if any) repeat (available (per 0.1 ml) injections** dose) 3. Dilute with 0.3 ml sterile water ??24–48 4. Inject 0.05 ml hours 10 Piperacillin/ 225 µg Data not available Data not tazobactam available (2.25 g) 11 Carbenicillin 2000 µg Data not available Data not (1 g) available 12 Ticarcillin 3000 µg Data not available Data not (with available clavulanate (3.1 g) 13 Aztreonam 100 µg Data not available 12 hours **All are in Phakic, nonvitrectomized eyes. Caution must be taken in interpreting the need for repeat intravitreals. Vitrectomized/aphakic eyes need more frequent injections whereas inflamed eyes have varied requirements.

Nuggets Caution should be taken to avoid mixing of drugs which may get precipitated, for eg, vancomycin and ceftazidime in a same syringe.

vi Labels for the antibiotics (for patient details), i In cases of subacute endophthalmitis with sus- to be used later. pected Propionibacterium acnes colonies seques- tered in the capsular bag, a 27G needle can be b. Procedure directly introduced from the opposite quadrant at the limbus, gently lifting the anterior capsule and i In continuation to the steps mentioned in 3b (i–vi). aspirating the sequestered organisms. ii Prepare the intravitreal injections fresh main- ii The intravitreal antibiotics can also be directly taining adequate sterility (Table 3). injected in the capsular bag behind the IOL iii Mix the drug thoroughly with a small air after gently lifting the anterior capsule with bubble to dissolve the antibiotic with solvent. the needle, taking care to inject small quan- tities and avoiding sudden injection (to prevent iv Remove the air completely and dispose the rupture of the capsular bag). excess drug to prepare the required amount. v In phakic/ pseudophakic eye: with 30G needle Nuggets directed toward the mid-vitreous cavity, enter 1. Initial broad spectrum empirical therapy is through pars plana (pars plicata in children less given based on the clinical evaluation or if a delay than 1 year age) and inject the required amount in the initial smear report is anticipated or if the fi of drug (loaded in 1 ml tuberculin syringe). initial report is equivocal. This should be modi ed immediately based on the microbiology study vi In aphakic eye: limbal entry with antibiotic results. injected into the vitreous cavity through the 2. The direct aspiration of capsular bag material anterior chamber. increases yield of organisms (e.g. Propionibacterium acnes). vii Apply cotton tip applicator to the injection site, examine the fundus and check eye pres- sure digitally. 5. Vitreous tap viii AC paracentesis may be needed if the IOP is high and a second injection is needed. a To be avoided (or performed with utmost care) in phakic non-vitrectomized eyes. ix Label the antibiotic vial and store in refriger- ator (do not freeze). b Indicated in recurrent/non-resolving endoph- thalmitis in a vitrectomized eye. x To be used within 3–5 days of preparation (either for topical or repeat intravitreals). c Use a sterile 27G needle with 2 cc or 5 cc syringe, enter through pars plana, aspirate gently (0.2– c. In the bag technique4 0.3 ml approximately), avoiding forceful suction.

66 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Preferred practice pattern

Table 4: Most common drugs used in endophthalmitis and their clinical profile11,12 Drug MOA Spectrum DOC for Emerging resistance

Cephalosporin Inhibit peptide Gram −ve cocci, Gram –ve Acinetobacter, Ceftazidime crosslinking of P. aeruginosa Anaerobes Enterococci Ceftriaxone polysaccharide Serratia (not active against Cefazolin chains of anaerobes), Gram +ve peptidoglycan; bacilli, Gram –ve bacilli, affects protiens in Enterobacter, E. coli cell membrane Klebsiella, proteus, H. influenzae, Gram +ve coci, Gram −ve bacilli, E. coli, Proteus, H. influenza Glycopeptide Inhibits the Gram +ve cocci, MRSA, MRSA Enterococci Vancomycin synthesis of MDR Staph epidermidis, precursor units of Clostridium, bacterial cell wall; Corynebacterium inhibits RNA diptheroids synthesis Aminoglycoside Blocks protein Second choice for Gram –ve Gram −ve Gram negative Bacilli Amikacin synthesis by bacilli, Pseudomonas, binding to 30S Enterobacter, klebsiella, subunit of E. coli, Serratia ribosomes Fluoroquinolones Topoisomerase II Broad spectrum against Gram −ve Enterococcus Ciprofloxacin inhibitors aerobic GPB, GNB, organisms faecalis, Moxifloxacin Pseudomonas, Gram +ve Streptococcus Streptococci, Staph. organisms pyogenes epidermidis, Actinomyces, Multi-drug resistant Nocardia sp. MTB, nososcomial Gram –ve, Gram +ve, Gram –ve anaerobes Polyenes Binds irreversible Aspergillus sp., Cryptococcus Individual strains of Amphotericin-B to ergosterol in cell Fusarium sp., neoformans Candida albicans, membrane which Demateciuos fungi Candida tropicalis, increases (Curvilaria, Bipolaris, Candida parapsilosis membrane Alternaria etc), Candida Fusarium sp. and permeability Sporothrix schenckii Triazoles Inhibition of Fusarium, candida, yeasts, Fluconazole Aspergilus fumigatus Voriconazole ergosterol filamentous fungi, resistant synthesis which Scedosporium candidemia increases apiospermum , Acremonium membrane permeability Carbapenem Inhibit cell wall Gram +ve, Gram –ve, Pseudomonas MRSA, pseudomonas Imipenem synthesis anaerobes aeruginosa, sp., Ticarcillin Prevent Gram –ve bacteria Enterococci Acinetobacter cross-linking of Pseudomonas baumannii, some peptidoglycan aeruginosa. Acinetobacter spp., during cell wall Bacteroides fragilis, synthesis and Enterococcus faecalis Enterobacteceae, H. influenzae MOA, mechanism of action; DOC, drug of choice; MRSA, methicillin-resistant Staphylococcus aureus; MDRS, multi-drug-resistant Staphylococcus; GPB, Gram-positive bacilli; GNB, Gram-negative bacilli d Keeping the same needle in situ (vitrectomized Nuggets eye tends to collapse after vitreous tap), the Vitreous tap is controversial in syringe is disconnected and antibiotic loaded non-vitrectomized eyes due to possibility of tuberculin syringe can be connected and vitreous traction and subsequent retinal injected to avoid repeat entry sites. detachment.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 67 Preferred practice pattern

Table 5: Doses of most commonly used antibiotics in management of Endophthalmitis13,14 Routes of administration Topical (1% = Subconjunctival Intravitreal Intravenous Infusiona Antibiotic 10 mg/ml) (mg) (per 0.1 ml) (µg/ml)

Ceftazidime 50 mg/ml 100–200 2.25 mg 2–6 g daily in 2–3 40–45 divided doses Cephazolin 50 mg/ml 100 2.25 mg 1–6 g daily in 3–4 – divided doses Vancomycin 25–50 mg/ml 25 1.0 mg 2 g daily in 2 doses 30–200 hydrochloride Clindamycin 50 mg/ml 15–50 1.0 mg 0.6–3.6 g daily in 3–4 9 divided doses Imipenem/ 5 mg/ml — 50–100 µg 2 g daily in 3–4 divided 16 Cilastatin doses sodium Ciprofloxacin 3.0 mg/ml 100 µg – Moxifloxacin 5.0 mg/ml 150–200 µg – Amikacin 20–50 mg/ml 25 125 µg 15 mg/kg/day in 2–3 8–10 (rarely used) (earlier divided doses 400 µg) Gentamycin 10–20 mg/ml 10–20 80 µg 3–5 mg/kg/day in 2–3 8 (rarely used) divided doses Piperacillin/ 6–20 mg/ml 100 225 µg 6–12 g every 4–6 hours – tazobactam Aztreonam — 100 100 µg – Ticarcillin 6–20 mg/ml 100 3000 µg 200–300 mg/kg daily in – disodium 4–6 doses Carbenicillin 4–6 mg/ml 100 2000 µg 15–30 g in 4–6 divided – doses Penicillin G 100,000– 0.5–1 million U – 2–18 million U daily in 80 200,000 U/ml 4–6 doses Tobramycin 10–20 mg/ml 10–20 100–200 µg 3–5 mg/kg daily in 2–3 10 sulphate doses Natamycin 5% Not indicated Not indicated Extremely toxic – suspension Amphotericin B 1–5 mg/ml 5–10 5 µg – 10–20 Voriconazoleb 10 mg/ml 10(Not used) 50 µg–100 6 mg/kg IV every 12 Not used µg hours (24 hours), then 4 mg/kg × 12 hours or 200 mg/day BD ‘–’ indicates data are not available. a Infusion: maximum prophylactic non-toxic doses, used per-operatively. b Shelf-life of most reconstituted antibiotics (fortified preparations) for topical use is 3–5 days except voriconazole, amikacin and tobramycin which has a shelf life of approximately 30 days

6. Vitreous biopsy vitrectomy. The syringe can be sent in a sterile container to the microbiology lab (Fig. 3). a Planned along with vitrectomy (20/23/25G). ii Intrector technique (Insight instruments, b Initial vitreous specimen without turning on Inc., Stuart, FL): one port vitrectomy (23G) the infusion fluid (undiluted sample). technique (portable, battery powered vitrec- tomy system), using the illumination from – c Approximately 0.3 0.5 ml of vitreous sample is the operating microscope or the indirect collected. ophthalmoscope,5 used for collection of vit- d Techniques reous sample as an office-based technique, in selective cases. i 5 ml syringe connected to suction port of fi vitrectomy cutter, gentle manual aspiration iii Microbiological evaluation of the lter applied by the assistant along with (rarely)/cassette used during vitrectomy.

68 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Preferred practice pattern

Nuggets ii Vitreous: Vitreous tap (see Point 5)/ Vitreous Correct placement of infusion cannula is biopsy (see Point 6). mandatory, so that infusion can be switched on as iii Others: IOL (with/ without bag contents), soon as the sample is collected, thereby avoiding the complications of hypotony. Blind cutting of IOFB, suture, abscised iris tissue, collection vitreous is to be avoided. from the vitrectomy cassette. iv After collection of sample, the air in the syringe is expelled and the needle is mounted into a sterile rubber cork placed in a large 7. Special situations sterile test tube container, sealed and sent to the laboratory for smear and culture (Fig. 3). a Pediatric/highly unco-operative patients: initial assessment can be followed by examination v In case of other material, the collected speci- under anesthesia, with AC tap, intravitreal men is to be sent in a sterile bottle without antibiotics/surgery in the same sitting. any solution or preservative. b Dose alterations: Vitrectomized eyes (increased b. Culture media (Fig. 4) frequency/daily injections intravitreally), sili- cone oil filled eyes (half dose injections intra- i For isolation of aerobic bacteria and fungi: vitreally, due to compartmentalization), 1 Solid media: blood agar, chocolate agar, pediatric age group (half volumes injected, due Macconkey agar, Sabouraud’s dextrose agar. to smaller globe volumes). 2 Liquid media: brain heart infusion broth. c Involvement of allied sub-specialties such as ii For isolation of anaerobic bacteria: cornea (for possible grafting in case of corneal/scleral involvement), glaucoma (if the 1 Solid media: Brucella blood agar. filtering bleb or the drainage device needs management) and an internist (in case of 2 Liquid media: thioglycollate broth. endogenous endophthalmitis). c. Inoculation and sending the samples to d Consent for evisceration to be taken in fulminant microbiology lab cases with detailed explanation to the patient and relatives prior to performing the surgery. i One drop each to be carefully inoculated (not to be spread) in agar media in the center of Nuggets the plate and into the Brain heart infusion Vitrectomy and/or lensectomy greatly decrease broth and thioglycolate broth. the half life of intraocularly administered drugs. ii It is essential that the inoculation of media is fl Ocular in ammation, however, can either increase done first (since the number of micro- or decrease the rate of elimination. organisms are likely to be low, every chance needs to be given to them to multiply and grow in the culture media) 8. Microbiology procedures and inoculation iii Growth for anaerobic micro-organisms and 6 methods fungus is observed for 12 days. a. Collection of intra-ocular samples iv Samples in odd hours may be inoculated in i Aqueous: AC tap (see Point 3). Brain heart infusion broth and thioglycollate

Figure 4. Commonly used solid and liquid culture media for inoculation of the samples.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 69 Preferred practice pattern

broth and kept at room temperature, 25–30°C is advised, and contra-indicated in fungal (with label). The remaining sample can also be endophthalmitis. capped onto the needle and kept in the refrigerator at 4°C compartment to be trans- Acknowledgements ported at the earliest (for PCR and making The authors thank Dr. Muna Bhende, Dr. Vikram smears). Koundanya, Dr. Vishvesh Agarwal from Shri Bhagwan Mahavir Vitreoretinal Services. They also thank entire team from Shri Bhagwan Mahavir Vitreoretinal Nuggets Services, Jadhavbai Nathmal Singhvee Glaucoma 1. The initial smear report should be obtained Services and L&T Microbiology Research Centre. at the earliest (within 45 minutes) 2. The initial smear reports consist of Gram’s References stain, and KOH/Calcoflour preparation 1. American Academy of Ophthalmology. Basic and Clinical 3. Growth of organisms in more than one plate Science Course: Section 12: Retina and Vitreous, 2004–5. is considered positive. Subsequently antibiogram San Francisco: American Academy of Ophthalmology, tests are conducted 2005:328–31. 4. Polymerase chain reaction (PCR) can detect 2. Safneck JR. Endophthalmitis: a review of recent trends. Saudi J the genomes of live as well as dead organisms, so Ophthalmol. 2012;26(2): 181–9. careful interpretation of the results should be made 3. Ang GS, Varga Z, Shaarawy T. Postoperative infection in and to be correlated clinically. penetrating versus non-penetrating glaucoma surgery. Br J Ophthalmol. 2010;94(12):1571–6. 4. Gopal L, Nagpal A, Verma A. Direct aspiration of capsular bag material in a case of sequestered Endophthalmitis. Indian J Ophthalmol. 2008;56(2):155–57. Endogenous endophthalmitis 5. Oshima Y, Kadonosono K, Yamaji H, Inoue M, Yoshida M, The common organisms implicated are Kimura H, Ohji M, Shiraga F, Hamasaki T; Japan Microincision Vitrectomy Surgery Study Group. Multicenter survey with a 1 Endocarditis: Staphylococcus aureus, systematic overview of acute onset Endophthalmitis after Streptococci (alpha, beta or gamma) transconjunctival microincision vitrectomy surgery. Am J Ophthalmol. 2010;150:716–25. 2 Liver abscess: Klebsiella pneumoniae 6. http://www.ijmm.org/documents/ocular.pdf. 7. Durand ML. Endophthalmitis. Clin Microbiol Infect. 3 Long-term hospitalization: Candida species 2013;19:227–34. (most common Candida albicans), and fila- 8. American Academy of Ophthalmology, section 12. Retina and mentous fungi (Aspergillus) rarely vitreous. pp 355–8. 2011–12. 9. Barry P, Cordovés L, Gardner S. ESCRS guidelines for Systemic antibiotics (antibacterials/antifungals) prevention and treatment of endophthalmitis following cataract play a key role in the management of endogenous surgery: data, dilemmas and conclusions. Paper presented at: endophthalmitis. Since the half-life of intravitreal the European Society of Cataract and Refractive Surgeons; 2013; antibiotics is short, the systemically administered Dublin, Ireland 10. Radhika M, Mithal K, Bawdekar A, Dave V, Jindal A, Relhan N, antibiotics are given to maintain therapeutic levels Albini T, Pathengay A, Flynn HW. Pharmacokinetics of for prolonged periods. The investigations includ- intravitreal antibiotics in endophthalmitis. J Ophthalmic ing the samples for microbiology tests should Inflamm Infect. 2014;10:22 ideally be sent before starting systemic antibiotics. 11. Bartlett JD, Jananus SD. Clinical Ocular Pharmacology, 4th edition. Butterworth-Heinemann, Boston. Role of systemic steroids 12. Ellis D. Amphotericin B: spectrum and resistance. J Antimicrob Chemother. 2002;49(Suppl. 1):7–10. Important in combating the intraocular inflamma- 13. Peyman GA, Duan M. Prophylaxis of endophthalmitis. tion that is particularly severe due to the release Ophthalmic Surg. 1994;25:67. of toxins from the infecting organisms. Caution in 14. Lemley CA, Han DP. Endophthalmitis: a review of current patients with diabetes and active Koch’s infection evaluation and management. Retina. 2007;27(6):662–80.

How to cite this article Verma A, Muralidharan V, Nigam E. Endophthalmitis: Current Trends, Drugs and Protocols, Sci J Med & Vis Res Foun 2015;XXXIII:61–70.

70 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

Macular Buckle in Myopia Pradeep Susvar and S. Vinay Kumar

Shri Bhagwan Mahavir Introduction Vitreoretinal Services, Pathologic myopia is one of the leading cause of Sankara Nethralaya secondary visual impairment worldwide and the most frequent cause in Asian subcontinent. Visual Correspondence to: impairment in these eyes with pathologic myopia Pradeep Susvar, is mainly due to the development of different Senior Consultant, types of myopic maculopathies, closely associated Shri Bhagwan Mahavir with the type and grade of the staphyloma.1 Vitreoretinal Services, Various authors have classified them into tessel- Sankara Nethralaya. lated fundus, lacquer cracks and patchy atrophy, E-mail: [email protected] diffuse chorioretinal atrophy, lacquer cracks, patchy chorioretinal atrophy, CNV, macular atrophy and posterior staphyloma.2 Macular hole with or without macular retinal detachments, myopic foveal schisis are established associations of the posterior staphyloma.1 These complications Fig. 1. are managed surgically by pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling with intraocular tamponade. Scleral short- History of macular buckle ening procedures, episcleral buckling are some of fi the additional procedures performed to take care 1957: Macular buckling was described for the rst of the posterior staphyloma component patho- time by Charles L. Schepens, the father of modern logical myopia with variable surgical success.3 retinal surgery, using a radially placed polyethyl- ene tube.6 1966: Rosengren B described a silver ring and plomb technique to indent the macula. The ring is Pathophysiology attached to the limbus and an arm fixed to the The pathogenesis of RD secondary to macular hole ring has a terminal ball, which was made to and retinoschisis in high myopia with posterior indent the macula. Photocoagulation is done after fl staphyloma are4,5 a day or two once the uid is absorbed. The ring and plomb are removed after 4 weeks.7,8 1 Posterior staphyloma leading to disparity in 1974: Theodossiadis used a silastic sponge rod the length of the sclera and retina (mismatch). placed between the inferior oblique insertion and 2 Anteroposterior traction caused by the the optic nerve. The rod was stretched vertically fi vitreous. across the macula by xing sutures to produce the required indentation. He followed his patients for 3 Tangential traction due to abnormal rigid ILM, upto 15 years.9 stretched retinal vessels or epiretinal 1980: Ando introduced the Ando plombe membrane. which is described in detail later.10, 11 Other possible explanations were weak adhe- sion between the neurosensory retina and retinal Evolution of surgical treatment for myopic pigment epithelium due to the severe myopic macular schisis, macular hole and RD chorioretinal atrophy and an incomplete detach- PPV with ILM peeling has been effective in terms ment of the posterior hyaloid that will increase of anatomical and functional success in the treat- the anteroposterior and tangential traction on the ment of macular schisis and macular holes asso- retina. ciated with high myopia.12–14 Complications The macular buckle is proposed to support the include formation or persistence of macular hole, posterior globe to counteract all the mechanisms macular hole retinal detachment (MHRD) and involved in such cases. Buckle changes the config- visual loss.15–16. Success of closure in these uration of the posterior pole from the concave myopic macular holes following surgery is less profile of posterior staphyloma to a plano/convex than the idiopathic holes in emmetropia.17 Ikuno protruding contour thereby relieving anteroposter- et al showed 25% of macular hole closure follow- ior traction, tangential traction and sclero retinal ing surgery in myopia with macular hole and mismatch (Fig. 1). foveoschisis with posterior staphyloma.18 Failure

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 71 Recent advances

of vitrectomy with ILM peeling in such cases lead adjustment of buckle height, a less accurate posi- to think about the other causative factors respon- tioning. The long-term safety of metal wire which sible for the macular complications in myopic eyes is embedded in the Ando’splombeisnotknown. with posterior staphyloma. Cases which had fail- ures following vitrectomy led one to consider add- itional or supplemental procedures which could T-shaped macular buckle {France Chirurgie negate the mismatch between the staphyloma and Instrumentation (FCI), Paris, France} retinal contour. This led to the surgical options of macular buckle in myopic eyes with posterior staphyloma

Indications The T-shaped macular buckle20 is created by • Myopic macular retinoschisis with posterior threading a 4-mm-wide solid silicone band pole staphyloma with recent decrease in visual through a 7-mm solid silicone macular wedge – ‘ ’ acuity. (Morin Devin T -shaped macular wedge) with a biconvex end. Macular wedge is negotiated under • Posterior pole detachment associated with the lateral rectus muscle, manoeuvred further to myopic macular hole with posterior staphyloma. be placed posteriorly under the staphyloma area. • Failed and recurrent cases of macular hole The 4-mm solid silicone bands are mobilized with or without RD following vitrectomy with under the vertical muscles, behind the obliques to or without tamponade. secure on to the nasal aspect, either side of the medial rectus. Advantages of T-shaped macular • Optic disc pit maculopathy. buckle are that it allows the adjustment for lengthening or shortening the band anteriorly Macular buckle types while sliding the macular plate in the coronal plane; it does not require posterior sutures or • Ando plombe direct access to the posterior pole, no need for • T-shaped macular buckle muscle disinsertion which carries the risk of post- operative pain and diplopia. Disadvantage • AJL macular buckle includes possibility of improper alignment under the fovea. • L-shaped macular buckle • Adjustable macular buckle AJL macular buckle • Wire-strengthened sponge exoplant

Ando’s plombe (Ondeko Corp)

Ando plombe consists of a T-shaped semirigid sili- cone rubber rod internally reinforced with titanium wires and an indenting head at one end. The length of the plombe is either 25 or 27 mm from head to tail, selected according to the size of globe. The size of the head is 4–5 mm. Mateo et al. AJL macular buckle is made up of PMMA material coupled Ando’splombewithaninternal30-G covered by silicone in order to increase its bio- optical fiber to enhance the visualization to place compatibility. It has an indentation area with a the indenting head correctly under the fovea.19 spherical helmet in its superior area to indent the Advantages include easy to insert the buckle, shape macular area. The arm’s length and curvature is memory, customization of buckle with its embed- customized depending on the patient’s specific ded wire and eliminates the need for sutures on the eye. It can be supplied with an optic fiber light staphylomatous sclera near macular area. probe for the accurate positioning of the head Disadvantages include its stiffness, limitations in under the fovea.

72 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

L-shaped macular buckle Wire-strengthened sponge exoplant

It consists of a 7 mm silicone sponge strengthened with a 0.5 mm orthodontic steel wire that is ori- ginally used for dental braces. First, the wire is bent into U shape at the middle with 2 mm separ- ation between the 2 arms. Then, the wire is inserted inside the sponge and fed through its whole length. The distal end is bent according to the eyes which help to indent the macula.23 L-shaped buckle is prepared using a silicone sponge (Labtician 507 oval sponge), 7 mm large and 5 mm thick and 3 cm long. A malleable titan- Limitations of macular buckle ium stent (Mod MCP6TP, Tekka, Pesaro, Italy) • Possible damage to nerves and vessels in the 15 mm long, 2 mm wide and 0.5 mm was inserted posterior pole. and hidden into the tunnel. The sponge could then be bent to obtain an L-shaped buckle by cre- • Precised alignment of the buckle under the ating a 90° angle to fashion the curvature accord- fovea is of concern. ingly. Advantages are that it can be easily • prepared in the operation theatre and the tech- Thin sclera increases the risk of perforation nique can be performed without the need of spe- and erosion is more. cially designed buckles, which are not available Precise alignment of the buckle under the fovea easily in all countries. Disadvantages include the can be achieved by either unknown long-term safety of the titanium inside • the orbit.21 External posterior landmarks. • Trans illumination.

Adjustable macular buckle (AMB) • Endo illumination. • Using illuminated optical fiber along with the macular buckle. We had an initial experience of three cases operated using the T-shaped macular wedge implants. Indications were recent central visual impairment due to progressive schisis, macular hole with macular detachment and persistent chorioret- inal mismatch at the staphyloma in an oil filled eye. One patient operated for the staphyloma asso- ciated macular hole with localized detachment, had the macular buckle along with vitrectomy, ILM peeling and tamponade. We noted the anatomical closure of the macular hole and the foveal attach- The AMB is made up of silicone rubber, consisting ment as early as fourth post-operative period. of a handle or stalk designed for radial positioning and a terminal plate intended to indent the macular area. Two lateral winglets at the terminal plate helps to pass suture through it. The two mer- silene sutures are brought on either side of the medial rectus, fixed to the sclera anterior to the equator. This procedure requires lateral rectus dis- insertion. Postoperatively the buckle effect can be adjusted using these sutures under local anaesthesia.22

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 73 Recent advances

Another case had a persistent lamellar hole with a 4. Ponozzo G, Mercanti A. Optical coherence tomography findings retinochoroidal mismatch post vitrectomy. This in myopic traction maculopathy. Arch Ophthalmol. 2004;122:1455–60. case was operated for the macular buckle alone in Ikuno Y, fi 5. Gomi F, Tano Y. Potent retinal arteriolar traction as a the oil lled eye. Patient had a progressive visual possible cause of myopic foveoschisis. Am J Ophthalmol. improvement with a gradual absorption of the 2005;139:462–7. subretinal fluid and the retinal apposition over a 6. Schepens CL, Okamura ID, Brockhurst RJ. The scleral buckling period of 5 months. Our initial short experience procedures. I. Surgical techniques and management. AMA Arch has been quite promising in terms of achieving Ophthalmol. 1957;58(6):797–811. anatomical restoration of the retina to match the 7. Rosengren B. The silver plomb method in macular holes. Trans 86 – contour of the ocular coats. Ophthalmol Soc UK. 1966; :49 53. 8. Rosengren B. The silver plomb method in amotio retinae: clinical experience and results. Bibl Opthalmol. 1966;70:253–6. 9. Theodossiadis G. Treatment of retinal detachment arising from macular hole. Mod Probl Ophthalmol. 1974;12:322–9. 10. Ando F. Use of special macular explant in surgery for retinal detachment with macular hole. Jpn J Ophthalmol. 1980;24:29–34. 11. Ando F. Improvement of surgical procedure for retinal detachment with macular hole and post-operative visual acuity. Jpn J Clin Ophthalmol. 1980;35:1179–83. 12. Kobayashi H, Kishi S. Vitreous surgery for highly myopic eyes with foveal detachment and retinoschisis. Ophthalmology. 2003;110:1702–7. 13. Kanda S, Uemura A, Sakamoto Y. Vitrectomy with internal limiting membrane peeling for macular retinoschisis and retinal Complications detachment without macular hole in highly myopic eyes. Am J Ophthalmol. 2003;136:177–80. The intraoperative complications include inadvert- 14. Ikuno Y, Sayanagi K, Ohji M, et al Vitrectomy and internal ent globe perforation, injury to vortex veins, ciliary limiting membrane peeling for myopic foveoschisis. Am J vessels and nerves, malposition of the buckle, optic Ophthalmol. 2004;137:719–24. nerve abutting, subretinal hemorrhage, choroidal 15. Benhamou N, Massin P, Haouchine B, et al Macular detachment and threatening suprachoroidal hemor- retinoschisis in highly myopic eyes. Am J Ophthalmol. 2002;133:794–800. rhage intraoperatively. Late complications include 16. Hirakata A, Hida T. Vitrectomy for myopic posterior buckle displacement, exposure, infection, choroidal retinoschisisor foveal detachment. Jpn J Ophthalmol. neovascular membrane progression, restriction of 2006;50:53–61. eye movements, diplopia, focal retinal pigment epi- 17. Mitry D, Zambarakji H. Recent trends in the management of thelium atrophy due to circulatory disturbances.24 maculopathy secondary to pathological myopia. Graefes Arch Clin Exp Ophthalmol. 2012;250(1):3–13. Conclusion 18. Ikuno Y, Sayanagi K, Oshima T, et al Optical coherence tomographic findings in macular holes and retinal detachment Macular buckle can be a good option for myopic after vitrectomy in highly myopic eyes. Am J Ophthalmol. posterior staphyloma-related macular conditions 2003;136:477–81. such as progressive macular schisis, macular hole 19. Mateo C, Medeiros MD. Micol illuminated ando plombe for and posterior pole RD. The technique requires optimal positioning in highlymyopic eyeswith vitreoretinal appropriate case selection and has a good anatom- diseases secondary to posterior staphyloma. JAMA Ophthalmol. ical and functional success as reported in many of 2013;131, Number 10 Devin F, the studies. Detection and correction of the reti- 20. Tsui I, Morin B, et al T-shaped scleral buckle for macular detachments in high myopes. Retina. 2011;31 noscleral mismatch would help improve functional (1):177–80. outcomes in these eyes with high myopia-related 21. Parolini B, Frisina R, Pinackatt S, et al A new L-shaped design maculopathy. of macular buckle to support a posterior staphyloma in high myopia. Retina. 2013;33(7):1466–70. References 22. Stirpe M, Ripandelli G, Rossi T, et al A new adjustable macular 1. Hsiang HW, Ohno-Matsui K, Shimada N, et al Clinical buckle designed for highlymyopic eyes. Retina. 2012;32 characteristics of posterior staphyloma in eyes with pathologic (7):1424–7. myopia. Am J Ophthalmol. 2008;146(1):102–10. 23. Mortada HA. A novel episcleral macular buckling: 2. Hayashi K, Ohno-Matsui K, Shimada N, et al Long-term pattern wire-strengthened sponge exoplant for recurrent macular hole of progression of myopic maculopathy: a natural history study. and retinal detachment in high myopic eyes. Med Hypothesis Ophthalmology. 2010;117(8):1595–611. Discov Innov Ophthalmol. 2013;2(1):14–9. 3. Bagolini B, Ravalico G. Surgical treatment of retinal 24. Siam AL, El Maamoun TA, Ali MH. Macular buckling for detachment with macular hole [Article in French]. Arch myopic macular hole retinal detachment: a new approach. Ophtalmol Rev Gen Ophtalmol. 1973;33:553–8. Retina. 2012;32:748–53.

How to cite this article Pradeep S, Vinay Kumar S. Macular Buckle in Myopia, Sci J Med & Vis Res Foun 2015; XXXIII:71–74.

74 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

Optical Coherence Tomography: Newer Techniques, Newer Machines

KP Mohana, Debmalya Das and Muna Bhende

Shri Bhagwan Mahavir Introduction SD-OCT scanning laser ophthalmoscopy systems Vitreoretinal Services, Since 1991, when optical coherence tomography Currently, the machines that are using the con- Sankara Nethralaya (OCT) was first introduced as a tool for investiga- focal scanning laser ophthalmoscopy (cSLO) tion in ophthalmology,1 OCT has become the system are the Optical Coherence Tomography Correspondence to: mainstay in retinal imaging and, in some situa- RS-3000 Advance from NIDEK, Cirrus HD-OCT Debmalya Das, tions, has supplanted fundus fluoresce in angiog- 5000 with FastTrac, OCT/SLO Combination Associate Consultant, raphy which is regarded, even today, as the gold Imaging System from Optos, OPKO Spectral OCT/ Shri Bhagwan Mahavir standard for investigations in choroidal and SLO Combo Imaging System and the Spectralis Vitreoretinal Services, retinal disorders. By definition, OCT represents a OCT. We will be discussing the Spectralis OCT in Sankara Nethralaya. non-invasive method for cross-sectional imaging details along with the added technologies for E-mail: [email protected] of the internal retinal structures through the better imaging. detection of optical reflections and echo time delays of light, using low coherence interferometry Spectralis OCT to subsequently produce in vivo two-dimensional Spectralis OCT (Heidelberg Engineering, images of internal tissue microstructure.1,2 Heidelberg, Germany) is a dual-beam SD OCT and Initially, the time domain (TD) technology was cSLO system that acquires transectional images or used (Stratus OCT, Carl Zeiss Meditec), which volume scans of the retina and an infrared refer- employed a mobile reference arm mirror that ence image simultaneously. A real-time eye sequentially measured light echoes from time tracker couples cSLO and SD OCT scanners to pos- delays with an acquisition speed of 400 A scans/ ition and stabilize the OCT scan on the retina second and axial resolution of 810 μm.2,3 TD OCT which leads to highly reproducible retinal thick- was limited by longer acquisition times (due to a ness measurements. High-speed imaging (40,000 mobile reference mirror), limited image sampling A scans/second) allows an increased number of (which potentially overlooked smaller lesions), acquired B scans resulting in greater retinal cover- motion artifacts and lack of patient cooperation.4,5 age and high-definition 3D images and more Fourier domain or spectral domain (FD/SD) detailed retinal thickness maps with less need of OCT succeeded the TD OCT. With a central wave- data interpolation in a short examination time. length of 800–850 nm, a stationary reference arm, The excellent reproducibility of retinal thickness a high-speed spectrometer, and a charge-coupled measurements with this technology can be attrib- device (CCD) line scan camera these OCTs had an uted to improved image resolution, imaging speed, increased acquisition speed of 25,000–52,000 A scan coverage, retinal segmentation algorithms scans/second, with axial resolution of 37 μm, sig- and to the eye tracking mechanism. To improve nificantly improved signal-to-noise ratio, reduc- the images, image averaging (Fig. 1) has been tion in motion artifacts, increased area of retinal used to achieve high-contrast and low-speckle coverage and better visualization of individual noise. Simultaneous real-time FFA and OCT and retinal layers.3 They were also able to create ICG and OCT is possible with this machine. three-dimensional (3D) topographic maps with precise registration.2 Imaging resolution and pene- Enhanced Depth Imaging tration was further enhanced by averaging and Spaide7 was the first to describe visualization of enhanced depth imaging (EDI). However, axial the choroid after moving the zero delay line deeper resolution and acquisition speed in SD OCT were into the eye, focusing the OCT scanner on the limited by the limitations of CCD line scan choroid instead of the retina. This is known as EDI cameras4,5 and SD OCT was still subject to motion OCT (Fig. 2). This technique has enabled the visual- artifacts, segmentation artifacts and interinstru- ization of structures lying deeper in the eye. ment comparability.3,5 Limited resolution due to infrared radiation En face OCT absorption by ocular structures, limited axial and ‘En face’ OCT (eOCT) imaging is an imaging tech- lateral resolution due to image scattering from ocular nique derived from SD OCT. It produces frontal sec- structures and restricted numerical aperture of the tions of retinal layers, also called ‘C-scan OCT’. optical system respectively, in both TD and SD OCT, Optical Coherence Tomography Retina Scan Duo were the major disadvantages that prompted from NIDEK, Zeiss Swept Source OCT (prototype, researchers to look for newer technologies.6 not yet FDA cleared) and deep range imaging

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 75 Recent advances

Fig. 1. (a) OCT image taken in Spectralis OCT showing CME and SRF. (b) Normal OCT scan with image averaging of 100 scans.

Fig. 2. EDI of a normal eye. Arrows indicate the Chorio-scleral interface.

(DRI)-OCT; Topcon Japan, are able to take ‘en face’ optical path and hence gives a better image when OCT. Optovue and Zeiss OCT also has frontal scans compared with the handheld OCT. However, it is adopted to retinal concavity and can take 3D and still limited by its 840-nm center wavelength and ‘En face’ OCT showing irregularities at ILM and lateral resolution.10 RPE layer. This novel technology offers a deeper The Rescan 700, Carl Zeiss, is a real-time insight into the understanding and follow-up of intraoperative SD-OCT that can be fully integrated macular diseases especially age-related macular into the OPMI Lumera 700 microscope. Key func- degeneration. Unlike conventional OCT, eOCT pro- tions of the OCT system can be controlled from cesses a series of transverse scans through tissue at the microscope’s foot pedal, so the surgeon can equally distributed and specific depths, determined take videos, snapshots and 3-D OCT images by modern optical sources capable of achieving without looking up or stopping the surgery. The depth resolutions upto 3 mm.8,9 Rescan allows the surgeon to see the surgical field in both a planar view and a cross-sectional view simultaneously, in real time. Haag-Streit’s intra- Intraoperative OCT operative iOCT system, developed by OptoMedical Microscope mounted OCT Technologies in Lübeck, Germany, attaches to the The use of intraoperative SD OCT help surgeons to camera port of the microscope; data are displayed better delineate tissue structures, reducing surgical on a screen mounted on the microscope. The times and limiting the need for potentially toxic 12 screen is also used to operate the system. The stains and excessive illumination. Microscope device follows the zoom and focus of the micro- fi mounted (MM) OCT can scan a 12-mm eld of scope so the scanned area matches the area being view by implementing a superluminescent diode viewed, and scans and images can be saved for with a center wavelength of 840 nm, allowing future review. Surgeons report that the device can real-time cross-sectional analysis of tissue struc- reveal structures to a depth of ∼4.2 mm in air and tures. MM OCT was designed to work with the 3.1 mm in water, with a resolution of ∼10 µm. optical path of the Oculus BIOM 3 suspended from a Leica M841 ophthalmic surgical microscope, and it provides a high magnification telescope Handheld OCT with a large field of view to the view port of the Ivue from Optovue and Bioptigen’s Envisu C2300 surgical microscope. MM OCT is stabilized and Spectral Domain Ophthalmic Imaging System are utilizes a common focal plane to the microscope designed for handheld or microscope-mounted use

76 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances for real-time imaging during ophthalmic surgical obtain 70,000 A scans/second. The Avanti procedures, compatible with most operating RTVue-XR can create 12 mm × 9 mm B scans, and microscopes. Stability of the instrument and hence its active eye tracking enhances image stability. the picture quality and maintenance of a sterile The Optovue system offers 3-µm digital resolution, surgical field remains and issue with handheld providing detailed imaging of both the choroid OCT. and the retina. Ultra-high-speed SS OCT, using a 1050– Swept source OCT 1060 nm FD mode locked laser, collects 1900 × 1900 A scans with a roughly 70° angle of view Swept source (SS) OCT utilizes a narrowband light (∼1cm2) in 36 seconds with image acquisition source with central wavelength of 1050 nm and speeds between 684,000 and 1,368,700 A scans/ with a short cavity swept laser (instead of a super second. These are then consolidated into a 4 mega- luminescent diode laser as in previous OCTs) that fi can emit different frequencies of light which are pixel high-de nition image. Good choroid and then rapidly tuned over a broad bandwidth.2,5,11 It choroidal/scleral interface penetration can also be achieved with axial resolution of 6.7–19 μm.13,14 uses a high-speed complementary metal oxide semiconductor (CMOS) camera (instead of a spec- trometer and CCD camera in conventional SD OCT) Adaptive optics OCT and two parallel photodetectors to achieve Adaptive optics corrects for higher-order ocular 100,000–400,000 A scan/second with 5.3-μmtissue aberrations during image acquisition, allowing axial resolution over a 4-mm imaging range. The improved lateral resolution and a near-cellular- small area, high-density imaging, extensive B scan level resolution.15,16 Ultra-high-resolution adaptive averaging, reduced fringe washout depth, longer optics OCT (AO OCT) uses a high-speed CMOS imaging range, higher detection efficiencies, and camera with a novel image registration/dewarping the ability to perform dual balanced detection algorithm to limit motion artifacts, increase lateral allows imaging down to the level of individual resolution, reduce speckle and enhance sensitiv- photoreceptors, particularly when coupled with ity.14 Ultra-high-resolution, AO, spectral-domain adaptive optics.5 These advantages also allow less OCT (UHR–AO–OCT) has an isotropic 3D resolution artifacts and better penetration through ocular of3×3×3μm3 in the retinal tissue. With a pupil media opacities. The long imaging range diameter of more than 6 mm, lateral resolution of (∼7.5 mm) also allows a better view of the vitreo- 23 mm can be achieved, which is sufficient for the retinal interface as well as the choroid in a single resolution of individual cones and of cross sec- frame with an enhanced sub-retinal pigment epi- tional profiles of individual retinal layers.14 In thelium (RPE) imaging without employment of EDI combination with an adaptive optics slit lamp (Fig. 3) or full-depth imaging. 4 However, it is still ophthalmoscope, AO OCT can acquire both OCT subject to some blur artifacts and image distor- and SLO in vivo with a resolution of 3.5 μm.16 tion.12 Improvements in dynamic retinal tracking and registration algorithms have helped to elimin- Optical microangiography ate some of these artifacts to allow improved reso- Optical microangiography (OMAG) technology lution. The DRI OCT-1 Atlantis and Zeiss SS-OCT utilizes an 840-nm wavelength with an A scan prototype (investigational device, not FDA cleared) rate of 27,000 Hz and an axial resolution of 8 μm are based on this system. 2 to image a 7.4 × 7.4 mm area of the posterior segment, allowing volumetric map acquisition.17 Widefield OCT OMAG in combination with widefield OCT can Widefield OCT employs swept source technology perform vascular perfusion mapping, down to the to evaluate larger portions of the central retina capillary level comparable to fluorescein and (Fig. 4). Optovue (Fremont, CA) Avanti RTVue-XR indocyanine green angiography. The technology, widefield system uses the SD technology and can though commercially available in Optovue

Fig. 3. Swept source OCT scan of a normal retina showing chorio-scleral interface clearly without EDI.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 77 Recent advances

Fig. 4. 12-mm OCT scan of proliferative diabetic retinopathy with vitreous hemorrhage done on (a) Swept source OCT revealing peripheral retinal traction which is missed on (b) a regular Spectral Domain OCT. Note the relative improvement in the visualization of the retinal surface on the Swept source OCT image even in the presence of media haze due to vitreous hemorrhage.

(Fremont, CA) RTVue-XR Avanti high speed, volumetric birefringence, contrasting between widefield and angiovue OCT system, currently has birefringent layers and other retinal layers.2,20,21 several limitations in terms of image quality in PS OCT simultaneously measures intensity (con- certain situations such as macular edema and ventional OCT images), retardation and optic axis atrophy and needs further refinement. orientation to distinguish polarization preserving tissue, birefringent tissue (Retinal nerve fiber Doppler OCT layer, Henle’s layer, sclera, fibrotic tissues) and Doppler OCT (D-OCT) is still under development, a polarization scrambling tissue (RPE).21 Light prototype. D-OCT, by measuring the Doppler shift transmitted through the RPE maintains the same and relative angle between the OCT beam and a polarization state and degree of retardation as blood vessel, assess the blood flow velocity.2,18 images below and above the RPE layer, allowing D-OCT (840 nm wavelength, axial resolution of 5 assessment of RPE damage.21 μm, transverse resolution of 20 μm) can measure fl retinal blood ow, and can detect any alteration Conclusion of the same even in the absence of any structural loss and hence opens up a new frontier in moni- With enhanced ability to image the choroid, retina toring and management of retinal and optic nerve and vitreous, our diagnostic capabilities are 18 greater than ever. These advancements have revo- vascular diseases and the patients at risk. Blood flow measurement can be accessed from the tran- lutionized ophthalmic practice over the last decade. Further innovations in both hardware and section of all branch retinal arteries and veins by software technologies are expected to aid in the eight circular scans, acquired in ∼2 seconds, each assessment of chorioretinal diseases in more detail composed of 3000 axial scans and then summing in future. OCT is here to stay. all blood flow measured in the veins. The back- ground axial inner retinal tissue boundary motion is compared with that of the vessel wall to attain References 19 the net Doppler shift, produced by blood flow. 1. Huang D, Swanson EA, Lin CP, et al. Optical coherence tomography. Science. 1991;254:1178–81. Polarization sensitive OCT 2. Duker JS. OCT technology: what is coming? Paper presented at Like D-OCT, polarization-sensitive (PS) OCT is a Annual Meeting of the European Society of Retina Specialists, Rome, Italy, January 28, 2012. prototype which can be used for functional tissue 3. Sull AC, Vuong LN, Price LL, et al. Comparison of spectral/ assessment by means of evaluation of light polar- Fourier domain optical coherence tomography instruments for ization which allows individual retinal layer iden- assessment of normal macular thickness. Retina. tification by measurement of cross-sectional and 2010;30:235–45.

78 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

4. Keane PA, Sadda SR. Imaging chorioretinal vascular disease. 13. Klein T, Wieser W, Eigenwillig CM, Biedermann BR, Huber R. Eye. 2009;24:422–7. Megahertz OCT for ultrawidefield retinal imaging with a 5. Potsaid B, Baumann B, Huang D, et al. Ultrahigh speed 1050 nm Fourier domain modelocked laser. Opt Express. 1050 nm swept source/Fourier domain OCT retinal and anterior 2011;19:3044–6. segment imaging at 100,000–400,000 axial scans per second. 14. Povazay B, Hermann B, Hofer B, et al. Widefield optical Opt Express. 2010;18:20029–48. coherence tomography of the choroid in vivo. Invest Ophthalmol 6. Wojtkowski M, Kaluzny B, Zawadzi RJ. New directions in Vis Sci. 2009;50:1856–63. ophthalmic optical coherence tomography. Optom Vis Sci 2012 15. Zawadzki RJ, Jones SM, Pilli S, et al. Integrated adaptive optics Mar 22. optical coherence tomography and adaptive optics scanning 7. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging laser ophthalmoscope system for simultaneous cellular spectral domain optical coherence tomography. Am J resolution in vivo retinal imaging. Biomed Opt Express. Ophthalmol. 2008;146:496–500. 2011;2:1674–86. 8. Podoleanu G., Dobre G.M., Webb D.J., Jackson D.A.. 16. Miller DT, Kocaoglu OP, Wang Q, Lee S. Adaptive optics and the Simultaneous en-face imaging of two layers in the human eye (super resolution OCT). Eye (Lond). 2011;25:321–30. retina by low-coherence reflectometry. Opt Lett. 1997;22 17. An L, Subhush HM, Wilson DJ, Wang RK. High-resolution (13):1039–41. Widefield imaging of retinal and choroidal blood perfusion with 9. Rogers J, Podoleanu A, Dobre G, et al. Topography and optical microangiography. J Biomed Opt. 2010;15:026011. volume measurements of the optic nerve using en-face 18. Sadda S. Future OCT technology. Paper presented at Macula optical coherence tomography. Opt Express. 2001;9: 2012, New York, NY, January 21, 2012. 533–45. 19. Wang Y, Lu A, GilFlamer J, Tan O, Izatt JA, Huang D. 10. Tao YK, Ehlers JP, Toth CA, Izatt JA. Intraoperative spectral Measurement of total blood flow in the normal human retina domain optical coherence tomography for vitreoretinal surgery. using Doppler Fourier domain optical coherence tomography. Br Opt Lett. 2010;35:3315–3317. J Ophthalmol. 2009;93:634–7. 11. Regatieri CV, Branchini L, Duker JS. The role of spectral domain 20. Michels S, Pircher M, Geitzenauer W, et al. Value of OCT in the diagnosis and management of neovascular age polarization-sensitive optical coherence tomography in diseases related macular degeneration. Ophthalmic Surg Lasers Imaging. affecting the retinal pigment epithelium. Br J Ophthalmol. 2011;42:S56–66. 2008;92:204–9. 12. Kocaoglu OP, Lee S, Jonnal RS, et al. Imaging cone 21. Yamanari M, Lim Y, Makita S, Yasuno Y. Visualization of photoreceptors in three dimensions and in time using ultrahigh phase retardation of deep posterior eye by polarization sensitive resolution optical coherence tomography with adaptive optics. swept source optical coherence tomography with 1 micron Biomed Opt Express. 2011;2:748–63. probe. Opt Express. 2009;17:12385–96.

How to cite this article Mohana KP, Das D, Muna B. Optical Coherence Tomography: Newer Techniques, Newer Machines, Sci J Med & Vis Res Foun 2015;XXXIII:75–79.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 79 Preferred practice pattern

Intravitreal Injection Guidelines Ekta Rishi and Pramod Bhende

Shri Bhagwan Mahavir With an increase in the number of intravitreal 1 Check the authorization letter of the bevacizu- Vitreoretinal Services, injections especially intravitreal anti-vascular mab dealer and buy the drug from a certified Sankara Nethralaya endothelial growth factor (anti-VEGF) agents the Roche dealer. Since the use in the eye is off risk for endophthalmitis is a potential concern. label, the dealers may not have the authoriza- 1 Correspondence to: A meta-analysis by Jager et al. shows that the tion for supply to the ophthalmologists. We Ekta Rishi, prevalence of endophthalmitis following intra- can inspect the authorization and bills from Senior Consultant, vitreal injections is low. They evaluated the Roche periodically. Shri Bhagwan Mahavir incidence of endophthalmitis into infectious and 2 Check the drug license of the dealer. Vitreoretinal Services, non-infectious categories and found that the Sankara Nethralaya. E-mail: [email protected] endophthalmitis rate was 0.9% (38/4382) per eye and 0.3% (38/14 866) per injection, when looking Cold chain lapse at both infectious and non-infectious cases. They Bevacizumab can be stored at 2–8°C for 45 days. also found endophthalmitis rate of 1.4% per injec- Roche monitors the cold chain on its server till it tion for intravitreal triamcinolone acetonide and transports to the authorized dealer. The company 0.2% per injection for intravitreal ranibizumab. also monitors and maintains a log of cold chain The risk of endophthalmitis after intravitreal at the storage facility of the dealer. injection may vary with various drugs.2 The reported Our suggestions incidence of endophthalmitis per patient in multi- • Inspect the cold chain maintenance of the center clinical trials with anti-vascular endothelial dealer. growth factor (VEGF) therapy ranged from 0.019 to 1.6%.2–4 Although cases of acute endophthalmitis • Verify that the drug has not been kept in stock following intravitreal bevacizumab (IVB) have for a long period. occurred, the exact incidence rate remains unknown. • Check how long does the dealer stocks the The injection technique and compounding issues drug. of bevacizumab remains the major areas of concern. Ranibizumab comes as a single use vial so the concerns are limited to injection techniques. Storage These guidelines are framed to reduce the risk Once purchased, check that the drug is brought in of endophthalmitis by streamlining the com- a dry ice pack preferably with a temperature mon- pounding and injection techniques with special itoring device. reference to bevacizumab. It should be stored at the hospital refrigerator The risk for endophthalmitis following at 2–8°C in a dark place with temperature display, Intravitreal Injections could be: power backup, and a temperature log. Electronic data loggers are available in the market to 1 Drug related: monitor the temperature. a Counterfeit medication The drug should be kept under lock so that b Lapse in cold chain limited people have the access to it and refriger- ator is not opened again and again to avoid a 2 Procedure related lapse in cold chain. a Multiple use of multi-dose vial Injection procedure related b Injection technique How to use the multi-dose vial of 4 ml? c Aseptic precautions The study by Bakri et al. shows that the drug can be kept in capped disposable 1 ml syringes Drug related when stored at 2–8°C with minimal loss of effi- This concern is more with off label drugs like cacy over 1 month, but there is no level 1 evi- bevacizumab. dence for sterility.6 There are published articles for compounding the drug in aliquots for multiple use Counterfeit medication but there are reports of endophthalmitis resulting There are reports of counterfeit medications across from compounding issues. the world for bevacizumab. In 2010–11, the We suggest opening a vial and preparing the concern was raised in China and the USA.5 required number of injections under sterile con- How to address and make sure that the drug is ditions and storing in different sterile boxes to be not fake? used within few hours if it has to be used by

80 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Preferred practice pattern different surgeons in different operation theatres 3 days of topical fluroquinolones or pulse dose on the same day within the same theatre complex. of fluroquinolone eye drops on the same day One box can be sent to each operation theatre of injection. with the required number of filled syringes. • We suggest that the injector has a proper scrub It is preferred to do the injection procedure in wears disposable mask, and gloves. If in oper- operation theater or a sterile room designated for ation theatre, cap is mandatory. such procedures.7,8 • The eye lids and lashes should be scrubbed with 10% povidone iodine solution and eye Preparation of multiple syringes for use on a should be draped. given day • Lid speculum should be used to avoid the • Note the batch number of the drug so that it contact of eye lashes with the injection site. can be helpful for tracking, in case of Use of lid speculum is reported to reduce the endophthalmitis. risk of endophthalmitis in the intravitreal • To check the bevacizumab vial for expiry date injection procedure. Contact of the needle with – and label by the technician. eyelashes should be avoided.13 15 • Opening of the vial and cleaning of rubber lid • Injection can be administered after the use of by alcohol wipes. sterile proparacaine eye drops. • 18/20 G needle is inserted in the rubber lid of • The needle used to cap the drug syringe for vial by a scrubbed paramedical staff in the storage should be replaced by a 30G needle for operation theatre with mask and cap with injection.16 minimal talking. Instead of using the 18/20G • Oblique scleral entry is preferred over perpen- needle for puncture an instrument called dicular injection to prevent reflux of vitreous mini-spike (Braun) can be used to prepare mul- and wick related endophthalmitis.16–19 tiple syringes to avoid contamination. • Any quadrant can be chosen for injection • The vial must be held upside down by non- (infero-temporal quadrant is preferred, particu- scrubbed personnel in the operation theater larly for opaque drugs which otherwise can wearing a cap and mask cause significant visual disturbance, e.g. triam- • The scrubbed staff can withdraw 0.2 cc of bev- cinolone). Sterile calipers can be used to acizumab in a 1 cc disposable syringe and cap measure 3–4 mm from limbus (depending on it with the needle. lens status) to mark the injection site. • Prepare the number of injections required for • Usage of mask is a must. Avoid talking while the day by withdrawing drug from a single giving the injection. Gram-positive cocci are puncture by 18/20G needle. the commonest infections following intra- vitreal injections and droplet infection may be • The prepared capped syringes with the drug the source.12,20,21 can be stored in separate boxes depending on the number of surgeons giving the injection on • The eye can be patched with povidone iodine the given day. The boxes can be kept in a 5% drops for 2 hours after injection. – refrigerator maintained at 2 8°C and should be • Patients should be examined on post injection used on the same day. day 1 and 3. We suggest a good examination • One syringe can be sent for bacterial culture of anterior segment using slit lamp and fundus sensitivity testing so that on follow-up of using indirect ophthalmoscopy. Also check these patients the report can help us to decide intraocular pressure using Applanation tono- the next plan of action in case of infection. metry. It is preferable to see the patient on the third post injection day as most of the • Preparation of similar aliquots in a sterile envir- endophthalmitis after bevacizumab have onment under a laminar hood is also described. occurred between 2 and 5 days. • Patients should be instructed to avoid head Injection technique bath for 1 day post injection and swimming • The literature suggests that prophylactic anti- for 3 days post injection. biotics are not better than the use of povidone • Post injection antibiotic prophylaxis should be iodine 5% drops for a contact period of reserved for one-eyed patients and patients 5 minutes in the conjunctival cul-de-sac.9–12 with doubtful hygiene or with iodine allergy. • Patients with doubtful hygiene, one eyed and Most of the studies suggest no role of antibio- with known povidone allergy, can have either tics in post injection period.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 81 Preferred practice pattern

• In case the patient is due for injection in both 8. Abell RG, Kerr NM, Allen P, Vote BJ. Intravitreal injections: is eyes, it should be done at an interval of 3 days there benefit for a theatre setting? Br J Ophthalmol. 2012;96 – to avoid an increased level of circulating drug (12):1474 8. 9. Cheung CY, Wong AT, Lui A, Kertes PJ, Devenyi RG, Lam WC. in the system. Some studies suggest that separ- Incidence of endophthalmitis and use of antibiotic prophylaxis ate batch number of the vials may be used for after intravitreal injections. Ophthalmology. 2012;119 the two eyes in case bilateral injections are (8):1609–13. required on the same day. 10. Kim SJ, Toma HS. Ophthalmic antibiotics and antimicrobial resistance: a randomized, controlled study of patients • Anti-VEGF injections should be deferred in undergoing intravitreal injections. Ophthalmology. pregnant ladies or people with uncontrolled 2011;118:1358–63. hypertension or increased risk of thrombo- 11. Bhat SB, Stepien KM, Joshi K. Prophylactic antibiotic use after embolic phenomenon or recent history of intravitreal injection: effect on endophthalmitis rate. Retina. 31 – stroke or myocardial infarction. 2011; :2032 6. 12. Moss JM, Sanislo SR, Ta CN. A prospective randomized • Injections should be avoided in people with evaluation of topical gatifloxacin on conjunctival flora in uncontrolled blood sugar levels as it may in patients undergoing intravitreal injections. Ophthalmology. 116 – turn increase the chances of endophthalmitis. 2009; :1498 501. 13. Green-Simms AE, Ekdawi NS, Bakri SJ. Survey of intravitreal injection techniques among retinal specialists in the United Discarding the unused drug States. Am J Ophthalmol. 2011;151(2):329–32. Fineman MS, It is preferable to discard the unused drug and 14. Hsu J, Spirn MJ, Kaiser RS. Bimanual assisted eyelid retraction technique for intravitreal injections. Retina. destroy the label. 2013;33(9):1968–70. The bottle can be discarded as per the norms. 15. Ratnarajan G, Nath R, Appaswamy S, Watson SL. Intravitreal injections using a novel conjunctival mould: a comparison with a conventional technique. Br J Ophthalmol 2013;l(4):395–7. References 16. Rodrigues EB, Grumann A Jr, Penha FM, Shiroma H, Rossi E, 1. Jager RD, Aiello LP, Patel SC, Cunningham ET Jr. Risks of Meyer CH, Stefano V, Maia M, Magalhaes O Jr, Farah ME. intravitreous injection: a comprehensive review. Retina. Effect of needle type and injection technique on pain level and 2004;24:676–98. vitreal reflux in intravitreal injection. J Ocul Pharmacol Ther 2. Scott IU, Flynn HW Jr. Reducing the risk of endophthalmitis 2011;27(2):197–203. following intravitreal injections. Retina. 2007;27:10–12. 17. Rodrigues EB, Meyer CH, Grumann A Jr, Shiroma H, Aguni JS, 3. Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Farah ME. Tunneled scleral incision to prevent vitreal reflux Chung CY, Kim RY, for the MARINA Study Group. Ranibizumab after intravitreal injection. Am J Ophthalmol. 2007;143 for neovascular age-related macular degeneration. N Engl J (6):1035–7. Med. 2006;355:1419–31. 18. Knecht PB, Michels S, Sturm V, Bosch MM, Menke MN. 4. Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Tunnelled versus straight intravitreal injection: intraocular Kim RY, Sy JP, Schneider S, for the ANCHOR Study Group. pressure changes, vitreous reflux, and patient discomfort. Ranibizumab versus verteporfin for neovascular age-related Retina. 2009;29(8):1175–81. macular degeneration. N Engl J Med. 2006;355:1432–44. 19. De Stefano VS, Abechain JJ, de Almeida LF, Verginassi DM, 5. Wykoff CC, Flynn HW Jr, Rosenfeld PJ. Prophylaxis for Rodrigues EB, Freymuller E, Maia M, Magalhaes O, Nguyen QD, endophthalmitis following intravitreal injection: antisepsis and Farah ME. Experimental investigation of needles, syringes and antibiotics. Am J Ophthalmol. 2011;152(5):717–9. techniques for intravitreal injections. Clin Experiment 6. Bakri SJ, Synder MR, Pulido JS, McCannel CA, Weiss WT, Ophthalmol. 2011;39(3):236–42. Singh RJ. Six month stability of Bevacizumab (Avastin) binding 20. McCannel CA. Meta-analysis of endophthalmitis after to vascular endothelial growth factor after withdrawal into a intravitreal injection of anti-vascular endothelial growth factor syringe and refrigeration or freezing. Retina. 2006;26:519–22. agents: causative organisms and possible prevention strategies. 7. Casparis H, Wolfensberger TJ, Becker M, Eich G, Graf N, Retina. 2011;31(4):654–61. Ambresin A, Mantel I, Michels S. Incidence of presumed 21. Wen JC, McCannel CA, Mochon AB, Garner OB. endophthalmitis after intravitreal injection performed in the Bacterial dispersal associated with speech in the setting of operating room: a retrospective multicenter study. Retina. intravitreous injections. Arch Ophthalmol. 2011;129(12): 2014;34(1):12–7. 1551–4.

How to cite this article Rishi E, Bhende P. Intravitreal Injection Guidelines, Sci J Med & Vis Res Foun 2015; XXXIII:80–82.

82 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

Recent Advancements in Ocular Electrodiagnostics Parveen Sen and Ramya Sachidanandam

Sri Bhagwan Mahavir Electrophysiology of the eye is a non-invasive Burian Allen electrodes in a light adapted state Vitreoretinal Services, method that allows functional assessment of retina after pupillary dilatation with refractive error cor- Sankara Nethralaya as well as the whole visual pathway. Although rection in place. Since testing is done in a light- there are many electrophysiological tests for asses- adapted state, the mfERG responses are primarily Correspondence to: Parveen sing function of retina and visual pathway, the fol- cone driven. It evaluates the function of fovea, Sen, lowing protocols play a major role in the diagnosis parafovea and perifovea using 103 alternating Senior Consultant, and management of retinal disorders. white and black hexagons. Sri Bhagwan Mahavir A typical mfERG waveform of the first-order 1 Full-field electroretinogram (ffERG). Vitreoretinal Services, kernel consists of an initial negative wave (N1) Sankara Nethralaya. followed by a positive peak (P1) (Fig. 1). These E-mail: [email protected] 2 Visual evoked potential (VEP) appear similar to the ffERG photopic ‘awave’ and 3 Electrooculogram (EOG). ‘bwave’, but they are not identical. 4 Multifocal electroretinogram (mfERG). The data are displayed in the form of three- dimensional topographic plots, group averages or 5 Multifocal visual evoked potential (mfVEP). trace arrays. Group averages and topographic plot 6 Pattern electroretinogram (PERG). evaluate the distribution of retinal signal. The three-dimensional plots should be seen with corre- 7 Photopic negative response (PhNR). sponding mfERG trace arrays for an accurate 8 Sweep VEP (sVEP) interpretation of results. Since mfERG is easy to interpret and well tolerated by the patient, it is International Society of Clinical Electrophysiology extensively used in various hereditary retinal dis- of Vision (ISCEV) has set standards for recording orders. In congenital maculopathies like each one of these tests except for photopic nega- Stargardt’s macular dystrophy and Vitelliform tive response and sweep VEP. macular dystrophy (VMD), the write foveal responses on mfERG are markedly diminished sur- Multifocal electroretinogram (mfERG) rounded by near-normal perifoveal responses. In Where ffERG is a mass electrical response gener- contrast in cone dystrophies, the mfERG-responses ated by retinal cells in response to a flash of light, across the entire retina are markedly decreased or mfERG stimulates various focal areas of the retina lost (Fig. 2). Role of mfERG in early stages of reti- and picks up focal disease as well as maps the notoxicity due to various drugs such as chloro- disease distribution. MfERG was developed by quine, hydroxychloroquine, deferoxamine and Erich Sutter.1 It is recorded monocularly using ethambutol is vital.2 It is now an integral part of

Fig. 1. Normal waveform of multifocal ERG.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 83 Recent advances

Fig. 2. mfERG trace array and 3-D plot multiplot (a) normal mfERG (b) Stargadt’s disease showing reduced foveal and parafoveal ring responses with normal perifoveal ring responses (c) Cone dystrophy showing generalized reduction of responses.

the new standard protocol for diagnosis of retinal especially in early glaucomatous neuropathy.4 The toxicity secondary to these drugs. MfERG can also PhNR is a slow negative potential that is seen be used as a tool for post treatment follow-up of after the b-wave of a light-adapted ffERG. The patients with choroidal neovascular membrane or background illumination and the stimulus color macular hole. are altered in the basic ffERG protocol to record MfERG plays little role in optic nerve disorders PhNR. It can be recorded as full-field PhNR, focal because the ganglion cells do not contribute to it. PhNR and mutifocal PhNR. The full-field PhNR reflects the overall retinal ganglion cell function Multifocal visual evoked potential (mfVEP) and is used to assess the generalized optic nerve Flash and pattern VEP evaluate the optic nerve func- damage while focal PhNR can reflect early 4 tion. Flash VEP is mass response and pattern VEP is damage. The PhNR is found to be decreased in dominated by responses from macular area. The primary open-angle glaucoma Fig. 4, ocular mfVEP as developed by Baseler et al.3 measures VEP hypertension and diabetic retinopathy. The PhNR responses from the focal areas of the visual field and amplitudes for red stimulus on blue background helps in picking up distribution of the optic nerve are large and are more effective in identifying 5 dysfunction. Interocular comparison of mfVEP early glaucomatous damage. recordings is a sensitive indicator of optic nerve disease (Fig. 3). MfVEP can also be done in subjects Pattern Electroretinogram (PERG) not cooperative for visual field testing and in PERG is helpful to differentiate between optic children. nerve disease and macular disorder.6 Transient PERG is produced by alternating reversal of a black Photopic negative response (PhNR) and white checkerboard pattern at a reversal rate of In addition to pattern VEP, PhNR has been used 6 per second. Normal transient PERG has two main as an indicator for ganglion cell function components: P50 (positive component appearing at

Fig. 3. MfVEP responses of 48-year-old female with pituitary adenoma and bitemporal hemianopia in HVF 30-2 showing bilateral non-recordable temporal waveforms.

84 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

Fig. 4. The amplitude of PhNR (photopic negative response) is reduced in a glaucomatous (b) eye as compared to a normal waveform (a).

45–60 ms) which shows macular function and disorder it does not give us the topography of the N95 (larger negative component appearing at disease process. 90–100 ms) which shows ganglion cell function Hence, a combination of these new investiga- (Fig. 5). PERG has very low amplitude (0.5–8 µV); tion modalities can give us a better understanding special care is needed to differentiate it from noise of the physiology of the various ocular diseases during recording. and help in their management. It is recorded binocularly using the DTL elec- trodes without pupillary dilatation with refractive error correction in place. Normal ffERG with decrease in P50 amplitude depicts localized macular dysfunction as seen in patients with Stargadt’s disease, macular hole and age related macular degeneration. An abnormal ffERG with an abnormal PERG suggests a generalized retinal disorder as is evident in cone rod dysfunction with macular involvement. Selective reduction of N95 component, with a near normal P50 wave suggests optic nerve pathology. N95/P50 ratio remains normal in macular disease but decreases in optic nerve diseases. During acute phase of optic neuritis a profound loss of visual acuity is seen with non-recordable PERG waveforms. In chronic phase of optic neuritis as the optic nerve edema resolves P50 recovers while N95 remains abnormal with significant reduction in the N95: P50 ratio. This is because of the retrograde degen- eration of the ganglion cells seen in the chronic stages of optic neuritis.7 Although PERG can dif- ferentiate between a retinal and an optic nerve

Fig. 6. Sweep VEP of nine different spatial frequencies. The calculated Minimal angle of resolution (MAR) based on amplitude values for different spatial frequencies (ranging from 3 to Fig. 5. Normal waveform of PERG showing N35, 32 cycles/degree) is 0.360 and the Snellen P50 and N95 components. visual acuity is 6/13.4.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 85 Recent advances

Sweep visual evoked potentials (sVEP) 2. Maturi RK, Yu M, Weleber RG. Multifocal electroretinographic The sVEP was introduced by Regan D (1973) for evaluation of long-term hydroxychloroquine users. Arch 122 – measuring refractive error objectively.8 It evaluates Ophthalmol. 2004; (7):973 81. 3. Baseler HA, Sutter EE, Klein SA, Carney T. The topography the visual acuity in infants, non-verbal and unco- of visual evoked response properties across the visual field. 9 operative children objectively. The sVEP has Electroencephalogr Clin Neurophysiol. 1994;90:65–81. many spatial frequencies that are swept in single 4. Viswanathan S, Frishman L, Robson JG, Walters JW. The recording session within 10–15 s of duration (Fig. photopic negative response of the flash electroretinogram in 6). By sweeping the spatial frequency from high to primary open angle glaucoma. Invest Ophthalmol Vis Sci. 42 – low, the visual acuity is obtained by determining 2001; :514 22. 5. Rangaswamy NV, Shirato S, Kaneko M, Digby BI, the highest spatial frequency to which the visual 10 Robson JG, Frishman LJ. Effects of spectral characteristics system responds. of Ganzfeld stimuli on the photopic negative response (PhNR) of the ERG. Invest Ophthalmol Vis Sci. Conclusion 2007;48:4818–28. 6. Bach M, Brigell MG, Hawlina M, Holder GE, Johnson MA, Various electrophysiological tests help in arriving McCulloch DL, Meigen T, Viswanathan S. ISCEV standard for at diagnosis and few tests help in the management clinical pattern electroretinography (PERG) – 2012 update. Doc of certain ocular diseases. mfERG assess retinal Ophthalmol. 2013;126:1–7. function in various retinal locations, mfVEP 7. Holder GE. The incidence of abnormal pattern assess focal areas of visual pathway function, electroretinography in optic nerve demyelination. Electroenceph 78 – PERG help in differentiating retinal and optic Clin Neurophysiol 1991; :18 26. 8. Regan D. Rapid objective refraction using evoked brain nerve disorders, PhNR helps to assess ganglion potentials. Invest Ophthalmol Vis Sci. 1973;12(9):669–79. cell function and sVEP is a objective quick 9. Tyler CW, Apkarian P, Levi DM, Nakayama K. Rapid assessment method to quantify visual acuity. of visual function: an electronic sweep technique for the pattern visual evoked potential. Invest Ophthalmol Vis Sci. 1979;18:703–13. References 10. Zhou P, Zhao MW, Li XX, Hu XF, Wu X, Niu LJ, Yu WZ, Xu XL. 1. Sutter E. Imaging visual function with the multifocal A new method for extrapolating the sweep pattern visual evoked m-sequence technique. Vision Res. 2001;41:1241–55. potential acuity. Doc Ophthalmol.2007;117(2):85–91.

How to cite this article Parveen S, Ramya S. Recent Advancements in Ocular Electrodiagnostics, Sci J Med & Vis Res Foun 2015;XXXIII:83–86.

86 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

Genetic Testing for Eye Diseases Vikas Khetan

Sri Bhagwan Mahavir Advances in ocular genetic research allows a Genotype–phenotype correlation for a few con- Vitreoretinal Services, better understanding of the genetic basis of many ditions have made us understand the diseases Sankara Nethralaya eye diseases. Genetic testing is becoming available much better. Knowing that a child with aniridia for more and more disorders and the number of has WAGR syndrome, we can be more vigilant in Correspondence to: genes being discovered is also on the rise, systemic work up. Vikas Khetan, although the testing may not be accessible to all Importance of genetic testing for Senior Consultant, because of the costs involved. Retinoblastoma cannot be overemphasized. Sri Bhagwan Mahavir Finding the genetic basis for a patient’s disease Children with germline mutation are at risk for Vitreoretinal Services, allows for risk prediction, accurate diagnosis, developing second non-ocular cancers and can Sankara Nethralaya. also pass the defective mutation to the offspring Email: [email protected] focused treatment and preventive screening and care. Personalized medicine, particularly in the and this could be explained to the family. For field of pharmacogenetics, is becoming a reality non-germline cases we can avoid unnecessary and we may be able to offer treatments to patients anesthesia exams. This can also be a big cost based on the genetic testing results. We do know saving for the family and can avoid unnecessary that some patients respond and some do not to long travels to specialized centers. the same anti-VEGF treatment for AMD/ PCV and At Sankara Nethralaya, we have now started part of this could be because of the genetic offering genetic testing for a lot of eye conditions makeup, therefore if we have the results with us after a pedigree-based counseling and the results before the start of the treatment, we may be able are then handed over to the patient after proper to decide better for the patient. However, genetic verification. The whole process takes around 4–6 testing for AMD is still in its infancy. months. With better understanding of retinal degenera- I would recommend all readers to read the tions, we now know that patients with ABCA4 article by Ed Stone et al. in ophthalmology about mutations should not be given Vitamin A prophy- recommendations for genetic testing of inherited laxis as it can worsen their disease. So with this eye diseases. knowledge the older practice of putting RP patients on vitamin A prophylaxis has reduced. Whilst there is no effective therapy that we can Reference offer to these patients, we should not cause a Stone EM, fi further decline in their visual status. Aldave AJ, Drack AV, Maccumber MW, Shef eld VC, Traboulsi E, Weleber RG. Recommendations for genetic testing of Gene therapy trials have taken place for RPE inherited eye diseases: report of the American Academy of 65 gene and for choroderemia and more trials are Ophthalmology task force on genetic testing. Ophthalmology in early phases. 2012;119(11):2408–10.

How to cite this article Vikas K. Genetic Testing for Eye Diseases, Sci J Med & Vis Res Foun 2015;XXXIII:87.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 87 Recent advances

Update on Intraocular Oncology Suganeswari Ganesan

Shri Bhagwan Mahavir Introduction wherein localized radiation is delivered to the base Vitreoretinal Services, Ocular oncology has been evolving with new of the intraocular tumor by surgically anchoring a Sankara Nethralaya imaging techniques and treatment modalities. radioactive-loaded plaque over the scleral surface. Imaging techniques have revolutionized the Plaque brachytherapy has evolved as an excellent Correspondence to: understanding of the basic concepts of the tumor alternative technique to enucleation sparing both Suganeswari Ganesan, pathology and have provided insights into the eye and vision. Consultant, development of newer modalities of treatment. In Vitreoretinal and Oncology the practice of Oncology, the primary focus has Intraocular tumors treated by brachytherapy with services, always been to save the life of the individual suf- recommended doses2 Sankara Nethralaya. fering from any carcinoma and this was also true E-mail: [email protected] Choroidal melanoma: 85 Gy for intraocular tumors with practicing ophthal- mologist needing to perform enucleation for most Retinoblastoma: 40 Gy of the intraocular tumors like the retinoblastoma Vasoproliferative tumors: 40 Gy in the children and choroidal melanoma in adults. With developments in ophthalmology and with Choroidal hemangioma: 40 Gy changing trends in diagnostic and management modalities, the attention has shifted from purely Brachytherapy team saving the lives to improving the quality of life. The quest to improve the quality of life in cancer Plaque surgeon survivors has led to the discovery of new techni- Radiation oncologist ques that can salvage the eye and the vision while simultaneously destroying the cancer tissue. In the Medical physicist most common pediatric cancer, the retinoblastoma the survival rates are nearly 100%. The success Commonly used isotopes in brachytherapy rates as per the International Classification of Retinoblastoma with standard intravenous chemo- Ruthenium (Ru)-106 reduction in group A (100%), B (93%), C (90%), D Palladium (Pd)-103 (48%), and E (25%).1 The eye salvage in retino- blastoma is achieved through the delivery of Iodine (I)-125 chemotherapy in various routes like the intraven- Strontium-90 (90Sr) ous, intra-arterial and intravitreal routes and the localized radiation therapy called the brachyther- apy. In the management of choroidal melanoma, brachytherapy plays a vital role in tumor regres- Photon Decay Half life (days) sion and also produces equivocal results when 125I Gamma 59.4 compared with enucleation (removal of the eye) in 103Pd Gamma 16.99 prevention of metastatic melanoma which was 131Cs Gamma 9.69 made evident by the Collaborative Ocular 106Ru Beta 371.8 Melanoma Study (COMS), conducted over a period 90 of 12 years. In the past three decades, we have Sr Beta 28.8 seen a revolution in conservative therapy with Dose calculation is done using the plaque simula- early detection of melanoma when the tumor tor software version (Bebig GmbH, Berlin, is 1–2 mm in thickness rather than detecting at Germany). The longitudinal, circumferential and 8–10 mm. In this update on intraocular oncology, apical diameters of the tumor are important para- we shall be discussing about some of the eye- meters to be measured using ultrasonography. sparing techniques like brachytherapy, intra-arterial chemotherapy and intravitreal chemotherapy. Structure of Indian plaque Indian plaque is manufactured by Bhabha Atomic Ophthalmic brachytherapy Research Center called ‘BARC I-125 Ocu-Prosta Definition seeds’. Radioiodine (125I) adsorbed on palladium- Brachytherapy (brachys, meaning ‘short-distance’) coated silver rod encapsulated by titanium is also known as internal radiotherapy. It found capsule.3 Slotted, unslotted, rimmed, unrimmed its use in ophthalmology in the year 1930. gold plaques are available. COMS plaques are cir- Ophthalmic brachytherapy is a surgical procedure cular rimmed plaques.

88 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

Fig. 1. Unslotted gold plaque in different sizes.

depression. Plaque containing the seeds is anchored to sclera. Conjunctiva is closed with sutures. Eye should be covered with lead shield and patient to be kept in isolation for a period of 4–5 days depending on the dosimetry.

Removal of plaque It is also performed under aseptic precautions as described above. Localized peritomy is made in the involved quadrant Anchoring sutures are cut. Plaque is removed with seeds in to. Seeds have to be counted and checked. Conjunctiva is closed with sutures. The radioactive seeds are returned back to Bhabha Atomic Research Center.

Fig. 2. BARC 125I Ocu-Prosta seeds. Limitations in choroidal melanoma • Tumor more than 12 mm in apical height or 20 mm in basal diameter.4 • Gross extraocular extension. • Painful blind eyes. • Eyes with no perception of light.

Complications of brachytherapy5

• Radiation cataract. • Radiation retinopathy. • Radiation optic neuropathy.

Intra-arterial chemotherapy (IAC) Definition Intra-arterial chemotherapy is a targeted therapy against retinoblastoma that involves the delivery Fig. 3. Plaque with the glued BARC 125I of potent chemotherapy directly into the ophthal- Ocu-Prosta seeds. mic artery.

Evolution Technique The first initiative was made in 1954 by Reese Placement of plaque et al.6 In 1966, Kiribuchi shared his success story It is performed under peribulbar or retrobulbar with injection of 5-fluorouracil into the frontal or anesthesia for adult patients and under general supraorbital artery of children with retinoblast- anesthesia for children. After cleaning, prepping oma.7 The technique of IAC has evolved over the and draping of the involved eye, localized perit- past 15 years with Japanese investigators showing omy is made in the involved quadrant. Tagging of success with delivery of melphalan into the oph- the rectus muscle is done. Localization of the thalmic artery by occluding distal flow in the tumor is done with transillumination or scleral internal carotid artery using catheterization and

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 89 Recent advances

Fig. 4. The pre- and post-brachytherapy of a medium sized choroidal melanoma with features of radiation retinopathy at 2 years.

balloon occlusion.8,9 Gobin and Abramson of the carotid artery using fluoroscopic guidance. Serial USA refined further by cannulating the proximal arteriogram is done for deciding the best ophthalmic artery precisely under fluoroscopic approach. Ipsilateral proximal portion of the oph- guidance for chemotherapy to perfuse the eye thalmic artery is catheterized with a microcatheter selectively without perfusing the brain.10 and a confirmatory angiogram is then performed. Chemotherapy is diluted in 30 ml of saline is Team delivered using a pulsatile, non-laminated tech- Ocular oncologist, endovascular neurosurgeon, nique manually over 30 min. Once the infusion is pediatric oncologist completed, a post-infusion arteriogram is done. The catheters are withdrawn and the femoral Japanese technique sheath is removed. By manual compression the hemostasis of the femoral artery is achieved. Child The Japanese technique was called selective oph- 12 thalmic arterial infusion (SOAI) therapy. The SOAI is kept on oral aspirin (40 mg) for 2 weeks. system consists of a micro-balloon, guiding cath- eter and a flushing hub. After selective catheter- ization to the cervical segment of the internal Dosage carotid artery by the guiding catheter, the micro- • balloon was propelled to the portion just distal to Melphalan: starting at 2.5 mg for 3 months to the orifice of the ophthalmic artery. During tem- 5.0 mg for a 3 years porary occlusion of the internal carotid artery, • Topotecan: starting at 0.3 mg for 3 months to melphalan was infused from the introduced cath- 0.4 mg for a 3 years eter tip.11 • Carboplatin: 30 mg for 6 months to 3 years American technique Performed under general anesthesia with anti- Eyes that would benefitfromIAC coagulation [intravenous heparin (75 IU/kg)] in • Primary IAC: International Classification of the operation theatre. Femoral region is cleaned, Retinoblastoma (group C , group D and group E) draped and 4-French arterial sheath is placed. The catheter is guided into the ipsilateral internal • Secondary IAC: other modalities have failed

90 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

Eyes that should not be considered for IAC with intravitreal injection of 8–30 μg melphalan and ocular hyperthermia for vitreous seeds. Since • Possibility of tumor regression with focal then melphalan hydrochloride, topotecan hydro- therapy (laser/trans pupillary thermotherapy/ chloride and methotrexate have been in use. cryotherapy) • Possibility of tumor regression with Team brachytherapy Ocular oncologist, anesthetist and pediatric oncologist. • Possibility of tumor regression with intraven- ous chemotherapy Dosage • Neovascular glaucoma 20–40 μg of melphalanhydrochloride15 8–20 μg of topotecan hydrochloride15 • Presence of invasion into the optic nerve • Presence of invasion into the choroid Technique It is performed under general anesthesia after • Presence of extrascleral extension cleaning and draping of the involved eye using a • Anaphylactic reaction with previous IAC sterile technique. Melphalan is available as a freeze-dried powder is prepared using the provided • Poor visualization of the tumor sterile diluent with concentration of 20 μg/0.1 ml. ∼ • Persistent retinal detachment The half-life is 90 min. Injected through the pars plana (3 mm from limbus, beveled approach) with a 30 G needle 1–2 clock hours away from the vit- 12 Complications from IAC reous seed cryotherapy is applied to the injection • Ophthalmic artery stenosis site to include the needle in the ice ball withdraw- ing the needle through the ice ball during the first • Occlusion of central retinal artery/ branch freeze. Triple freeze thaw cryotherapy is then com- retinal artery occlusion/ciliary arteries pleted. The eyeball should be moved with forceps • Orbital vascular occlusion vigorously to cause drug dispersion throughout the vitreous cavity and preferably to the site of • Eyelid edema vitreous seeds. • Blepharoptosis Eyes that would benefit • Cilia loss Persistent/recurrent/viable vitreous retinoblastoma seeds with good regression of the solid tumor.16 • Orbital congestion • Temporary extraocular dysmotility Eyes that should not be considered for intravitreal chemotherapy • Retinal pigment epithelial mottling • Presence of viable solid intraretinal • Radiation-related toxic effects retinoblastoma • Concern Presence of viable viable subretinal seeds • Presence of uveal or optic nerve invasion • Anomalous origin of the ophthalmic artery • Risk for metastatic disease • Blood dyscrasia

Intravitreal injections in intraocular oncology Complications Definition • Focal retinal pigment epithelial mottling Intravitreal chemotherapy is a targeted therapy • Risk for extraocular subconjunctival extension against retinoblastoma seeds in the vitreous that involves the delivery of potent chemotherapy dir- • Vitreous hemorrhage ectly into the vitreous. • Retinal detachment • Evolution Intraocular infection Ericson et al.13 were the first to initiate the intra- vitreal chemotherapy for retinoblastoma in the Conclusion year 1960. The superior efficacy of melphalan was Developments in intraocular oncology have been established by Inomata and Kaneko.14 Later, overwhelming in the past three decades with Kaneko presented his unpublished data on achiev- excellent responses to conservative treatment in ing eye salvage rate of 51% by treating 41 eyes both retinoblastoma and choroidal melanoma.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 91 Recent advances

Solid tumors in retinoblastoma have shown good 6. Reese AB, Hyman GA, Merriam GR Jr, et al. Treatment of regression patterns with chemotherapy/focal retinoblastoma by radiation and triethylenemelamine. AMA 53 – thermal laser/localized brachytherapy. Subretinal Arch Ophthalmol. 1954; (4):505 13. 7. Kiribuchi M. Retrograde infusion of anti-cancer drugs to tumor seeds show partial or complete response to ophthalmic artery for intraocular malignant tumors [in therapy. Vitreous seeds are the least responsive Japanese]. Nippon Ganka Gakkai Zasshi. 1966;70:1829–33. and remain a major challenge. Management of 8. Yamane T, Kaneko A, Mohri M. The technique of ophthalmic small choroidal melanoma by observation or arterial infusion therapy for patients with intraocular plaque radiation therapy remains controversial. retinoblastoma. Int J Clin Oncol. 2004;9(2):69–73. Medium choroidal melanoma is better managed 9. Suzuki S, Kaneko A. Management of intraocular retinoblastoma and ocular prognosis. Int J Clin Oncol. 2004;9 by brachytherapy as brachytherapy yields equi- – fi (1):1 6. valent overall and melanoma metastasis-speci c 10. Gobin P, Abramson D. A phase I/II study of intra-arterial survival rates to enucleation for medium-sized (ophthalmic artery) chemotherapy for intraocular melanomas. Large choroidal melanoma manage- retinoblastoma [abstract 60]. J Vasc Interv Radiol. 2008;19 ment still remains a challenge in terms of eye (suppl 2):s24–5. sparing techniques. 11. Yamane T, Kaneko A, Mohri M. The technique of ophthalmic arterial infusion therapy for patients with intraocular retinoblastoma. Int J Clin Oncol. 2004;9(2):69–73. References 12. Shields Carol L., Manjandavida Fairooz P., Lally Sara E. 1. Shields CL, Mashayekhi A, Au AK, et al. The International Intra-arterial chemotherapy for retinoblastoma in 70 eyes Classification of Retinoblastoma predicts chemoreduction outcomes based on the International Classification of success. Ophthalmology. 2006;113(12):2276–80. Retinoblastoma. Ophthalmology. 2014;1–8. 2. The American Brachytherapy Society – Ophthalmic Oncology 13. Ericson LA, Kalberg B, Rosengren BH. Trials of intravitreal Task Force. The American Brachytherapy Society consensus injections of chemotherapeutic agents in rabbits. Acta guidelines for plaque brachytherapy of uveal melanoma and Ophthalmol. 1964;42(4):721–6. retinoblastoma. American Brachytherapy Society (2013). 14. Kaneko A, Suzuki S. Eye-preservation treatment of 3. Khetan V, Gopal L, Shanmugam MP, et al. Brachytherapy of retinoblastoma with vitreous seeding. Jpn J ClinOncol. 2003;33 intraocular tumors using ‘BARC I-125 Ocu-Prosta seeds’:an (12):601–7. Indian experience. Indian J Ophthalmol. 2014;62(2):158–62. 15. Shields CL, Manjandavida FP, Arepalli S, et al. Intravitreal 4. Shields CL, Naseripour M, Cater J, et al. Plaque radiotherapy for melphalan for persistent or recurrent retinoblastoma vitreous large posterior uveal melanomas (O or 58-mm thick) in 354 seeds: preliminary results. JAMA Ophthalmol. 2014;132 consecutive patients. Ophthalmology. 2002;109:1838–49. (3):319–25. 5. Puusaari I, Heikkonen J, Kivelä T. Ocular complications after 16. Ghassemi F, Shields CL. Intravitreal melphalan for refractory or iodine brachytherapy for large uveal melanomas. recurrent vitreous seeding from retinoblastoma. Arch Ophthalmology. 2004;111:1768–77. Ophthalmol. 2012;130(10):1268–71.

How to cite this article Suganeswari G. Update on Intraocular Oncology, Sci J Med & Vis Res Foun 2015;XXXIII: 88–92.

92 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Review article

Retinopathy of Prematurity: An Update

Parveen Sen, Chetan Rao and Nishat Bansal

Sri Bhagwan Mahavir Introduction 1 ml of 10% phenylephrine (Drosyn) mixed in 3 ml Vitreoretinal Services, Retinopathy of prematurity (ROP) was originally of 1% tropicamide (after discarding 2 ml from 5 ml Sankara Nethralaya designated as retrolental fibroplasias by Terry in bottle) for pupillary dilatation. These combination 1952 who related it with premature birth.1 Term drops are used every 15 minutes for 3 times. 2 Correspondence to: ROP was coined by Heath in 1951. Punctum occlusion is mandatory after instilling the Parveen Sen, It is a disorder of development of retinal blood drops to reduce the systemic side effects of medica- Senior Consultant, vessels in premature babies. Normal retinal vascu- tion. Excess eye drops should also be wiped off to Sri Bhagwan Mahavir larization happens centrifugally from optic disc to prevent absorption through cheek skin. If the pupil Vitreoretinal Services, ora. Vascularization up to nasal ora is completed does not dilate in spite of proper use of medication, Sankara Nethralaya. by 8 months (36 weeks) and temporal ora by 10 presence of plus disease should be suspected. E-mail: [email protected] months (39–41 weeks).3 Repeated installation of topical drops should be The incidence of ROP is increasing in India avoided to prevent systemic problems. Sterile because of improved neonatal survival rate. Out of Alfonso speculum is used to retract the lids and wire 26 million annual live births in India, approxi- vectis for gentle depression. mately 2 million are <2000 g in weight and are at High-quality retinal images obtained using risk of developing ROP.3 In India the incidence of commercially available wide-angle fundus camera ROP is between 38 and 51.9% in low-birth-weight like the Retcam followed by Telescreening by a infants.3,4 trained ophthalmologist can also be done. In developing countries like India where majority of Screening guidelines people live in remote areas which may not have American Academy of Pediatrics guidelines5 access to the tertiary-level care, telescreening may bring more children into the screening program. • Infants with birth weight of ≤1500 g. This model has been successfully used by Vinekar • Gestational age of 30 weeks or less. et al. in Karnataka Internet Assisted Diagnosis of Retinopathy of Prematurity (KIDROP).6 The follow • Infants with birth weight between 1500 and up schedule for these babies is given in Table 1. 2000 g or gestational age of >30 weeks with unstable clinical course. Role of laser Since the stimulus for abnormal vessels comes Indian scenario4 from the avascular retina therefore ablating the • Birth weight <1700 g peripheral avascular retina is believed to cause regression of the ROP. Earlier the CRYO-ROP • Gestational age at birth <34–35 weeks Study7 treatment guidelines were followed; with the results of Early treatment for retinopathy of • Exposed to oxygen >30 days prematurity (ETROP study)8 there has been a para- • Infants born at <28 weeks and weighing digm shift in treatment to laser therapy from <1200 g are particularly at high risk of devel- CRYO therapy. Laser therapy significantly allows oping severe form of ROP more precision of treatment as well as reduces the unfavorable side effects of the cryotherapy and • Presence of other factors such as respiratory has more than 90% successful results.8 Laser treat- distress syndrome, sepsis, multiple blood trans- ment protocol according to ETROP is given in fusions, multiple births (twins/triplets), apneic Table 2. episodes, intraventricular hemorrhage increase risk of ROP. In these cases screening should be Treatment guidelines considered even for babies>37 weeks gestation Laser is done using indirect laser ophthalmoscope or >1700 g birth weight. under topical anesthesia after pupillary dilatation The first screening should be done within 4 weeks under care of an anesthetist in the operation (30 days) of life in infants with age >28 weeks of theatre. The entire avascular retina up to the ora gestational age. Screening should be done earlier serrata should be ablated with near confluent (2–3 weeks after birth) if gestational age is <28 weeks burns (0.5–1 burn width apart) up to the ridge. or birth weight is <1200 g.4 Screening should be Heart rate and apnea spells should be monitored done by an ophthalmologist who is well versed throughout the laser.9 In severe forms of disease with indirect ophthalmoscopy in ROP babies. Child not responding to this laser photocoagulation should be fed 1 hour prior to examination. We use further laser to the ridge as well as posterior to

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 93 Review article

Fig. 1 (A) Stage 1: Demarcation line. (B) Stage 2: Ridge. (C) Stage 3: Ridge with extra retinal fibrovascular proliferation. (D) Stage 4A: extrafoveal retinal detachment. (E) Stage 4B: fovea involving retinal detachment. (F) Plus disease with dilated and tortuous retinal vessels

Table 1 Follow-up schedule for ROP babies4 Follow-up Immature vascularization, ROP ROP Regressing no ROP Stage 1 or 2 Stage 3 ROP

1 week or Zone I or immature retina Stage 1 or 2, Zone III, zone II less extends into posterior zone II zone I pre-threshold 1–2 weeks Posterior zone II Stage 2, zone II Unequivocally regressing ROP, Zone I 2 weeks Zone II Stage 1, zone II Unequivocally regressing ROP, Zone II 2–3 weeks Stage 1 or 2, Regressing ROP, Zone III zone III

ridge has also been shown to be effective in severe Follow-up visits after laser treatment are cases of ROP.10 This has caused regression of the usually weekly till the ROP regresses and involu- disease in some cases and avoided the progression tion of all tractional elements is seen and vascu- of tractional retinal detachment. larization reaches the temporal ora.

94 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Review article

Table 2 Laser treatment protocol for ROP according 3 Failed laser treatment leading to persistent to ETROP8 neovascularization, tractional elements or trac- Zone 1 tional retinal detachment prior to surgery. No Plus Stage 1 Follow Stage 2 Follow Role of surgery Stage 3 Treat Surgery is done for tractional retinal detachment Plus Stage 1 Treat (TRD) repair as seen in Stages 4 and 5 ROP. The Stage 2 Treat aim for surgical intervention in Stage 4 ROP is to Stage 3 Treat prevent progression of retinal detachment. Scleral Zone 2 buckling (placing 240 band at the height of the No Plus Stage 1 Follow TRD by making sclera tunnels in all quadrants) is Stage 2 Follow done for Stage 4A ROP with only peripheral trac- Stage 3 Follow tional retinal detachment. This surgery does not Plus Stage 1 Follow involve the removal of membranes formed on the Stage 2 Treat retina but by causing peripheral scleral indenta- Stage 3 Treat tion reduces the effective TRD. This procedure can be combined with cryotherapy or laser to any peripheral persistent new vessels. The encircling Role of anti-vascular endothelial growth band needs to be removed once the child is 1 year factor (VEGF) of age to allow normal growth of the eyeball and In recent times, anti-VEGF has also been used in to reduce the amount of anisometropia induced by severe forms of ROP, especially those not respond- the buckle. ing to laser photocoagulation. Its role, however, is Lens sparing vitrectomy (LSV) has shown very controversial. VEGF is needed in premature promising results in Stages 4A and 4B. Long-term babies for the normal organogenesis and vasculo- results with lens sparing vitrectomy were favor- genesis. Also systemic absorption may cause vas- able in the study by Trese et al.: 82.1% (Stage 4A), cular development delay in other organs in these 69.5% (Stage 4B) and 42.6% (Stage 5) showing premature babies. Therefore, it is not recom- successful anatomical reattachment of retina with 5 mended by many as the first-line therapy. lens being clear for at least the first decade of BEAT ROP study which compared bevacizumab life.14 Bhende et al. also reported 82% anatomical monotherapy with conventional laser therapy success in 4A stage ROP and 50% in Stage 4B showed promising results for stage 3+ ROP in ROP after single procedure.15 25-Gauge vitrectomy 11 zone 1 but not in zone 2. In this study, periph- is now commonly used for ROP surgery. Finer eral retinal vessels continued in normal fashion instrumentation and more effective microvit after treatment with intravitreal bevacizumab. This systems in small gauges are useful during mem- study was too small to assess the safety profile in brane dissection. However, modification of the 11 these babies. technique in the form of conjunctival dissection The follow-up period after mono therapy is as well as suturing of the sclerotomies at the end unpredictable as there can be a recurrence of neo- of surgery may be necessary.16 Modern vitreo- vascularization even beyond 54 weeks of post- retinal surgical tools like the infusion light pipe, gestational age. It is recommended that follow-up binocular indirect ophthalmoscopy (BIOM) which should be continued till there is no evidence of allows wide-angle viewing has reduced the risk of tractional elements and the vascularization creating iatrogenic retinal breaks and also sparing 5 reaches ora. In Zone 1 ROP, the Laser treatment of lens, allowing easy visual rehabilitation in outcomes are poorer. Treatment with anti-VEGF these children.17 followed by a 4–5 days later with laser treatment In Stage 5 ROP, the results of surgical interven- in these cases has improved the efficacy of laser tion are poor. It usually involves the removal of along with a reduced need for extensive laser the lens. Gopal et al. had anatomical success with 12 especially at the posterior pole. In a study by the attachment of posterior pole in 22.5% of cases Chen et al. both bevacizumab and ranibizumab with lens sacrificing vitrectomy though visual had similar efficacy at the end of 1 year in terms results were unsatisfactory with only two children 13 of ROP regression and visual acuity. showing mobile vision out of 96 eyes.18 Closed On the basis of available literature indication globe vitreoretinal surgery was done in all these for anti-VEGF therapy can be enumerated as: eyes with Stage 5 ROP. The aim of the surgery for Stage 5 ROP is to clear all preretinal tissue up to 1 Primary therapy for aggressive posterior zone the disc and open the peripheral trough all round. 1 disease (APROP). In most instances, bimanual surgery under visco- 2 Aggressive anterior ROP or media haze due to elastic is performed. Anterior chamber (AC) main- aggressive posterior disease to improve visual- tainer to keep the IOP under control during ization for laser treatment. surgery is also used. Fixation of infusion cannula

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 95 Review article

through pars plicata is impossible in these cases prematurity: results of early treatment of retinopathy of because the retina is pulled up to the lens. prematurity randomized trial. Arch Ophthalmol. 121 – Open sky vitrectomy (through a trephined 2003; :1684 96. 9. Jalali S, Azad R, Trehan HS, Dogra MR, Gopal L, Narendran V. corneal opening) has also been advocated by some Technical aspects of laser treatment for acute retinopathy of 19 especially in cases with corneal opacity. It has prematurity under topical anesthesia. Indian J Ophthalmol. the advantage of allowing two hand dissection 2010;58(6):509–15. from a large anterior incision but maintenance of 10. Uparkar M, Sen P, Rawal A, Agarwal S, Khan B, Gopal L. Laser intraocular pressure is difficult. photocoagulation (810 nm diode) for threshold retinopathy of prematurity: a prospective randomized pilot study of treatment Conclusion to ridge and avascular retina versus avascular retina alone. Int Ophthalmol. 2011;31(1):3–8. Considering the poor outcome of surgery in end- 11. Mintz-Hittner HA, Kennedy KA, Chuang AZ; BEAT-ROP stage ROP timely intervention in the form of laser Cooperative Group. Efficacy of intravitreal bevacizumab for treatment is the best treatment option. There is stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364 need to increase the awareness of the disease to (7):603–15. make sure these babies can be treated on time. 12. Mota A, Carneiro A, Breda J, Rosas V, Magalhaes A, Silva R, Also there is a need of more numbers of special- Falcao-Reis F. Combination of intravitreal ranibizumab and ized vitreoretinal surgeons who can handle these laser photocoagulation for aggressive posterior retinopathy of prematurity. Case Rep Ophthalmol. 2012;3(1):136–41. babies. 13. Chen SN, Lian I, Hwang YC, Chen YH, Chang YC, Lee KH, Chuang CC, Wu WC. Intravitreal anti-vascular endothelial References growth factor treatment for retinopathy of prematurity: 1. Terry TL. Extreme prematurity and fibroblastic overgrowth of comparison between ranibizumab and bevacizumab. Retina. persistent vascular sheath behind each crystalline 2015;35(4):667–74. lens. I. Preliminary report. Am J Ophthalmol. 1942;25:203–4 14. Nudleman E, Robinson J, Rao P, Drenser KA, Capone A, 2. Heath P. Pathology of retinopathy of prematurity, RLF. Am J Trese MT. Long-term outcomes on lens clarity after lens-sparing Ophthalmol. 1951;34:1249–68. vitrectomy for retinopathy of prematurity. Ophthalmology. 3. Pejawar R, Vinekar A, Bilagi A. National Neonatology 2015;122(4):755–9. Foundation’s Evidence-based Clinical Practise Guidelines 15. Bhende P, Gopal L, Sharma T, Verma A, Biswas RK. Functional (2010), Retinopathy of Prematurity, NNF India, New Delhi and anatomical outcomes after primary lens-sparing pars plana 2010:253–62. vitrectomy for Stage 4 retinopathy of prematurity. Indian J 4. Jalali S, Anand R, Kumar H, Dogra MR, Azad R, Gopal L. Ophthalmol. 2009;57(4):267–71. Programme planning and screening strategy in retinopathy of 16. Gonzales CR, Boshra J, Schwartz SD. 25-Gauge pars plicata prematurity. Indian J Ophthalmol. 2003;51(1):89–99. vitrectomy for stage 4 and 5 retinopathy of prematurity. Retina. 5. Fierson WM. Screening examination of premature infants for 2006;26(7 Suppl):S42–6. retinopathy of prematurity. Pediatrics. 2013;131:189–95. 17. Trese MT, Capone A Jr. Surgical approach to infant and 6. Vinekar A, Gilbert C, Dogra M, Kurian M, Shainesh G, Shetty B, childhood retinal diseases: invasive methods. In Hartnett ME, Bauer N. The KIDROP model of combining strategies for Tresse MT, Capone A Jr, et al, eds. Pedatric Retina. Philadelphia: providing retinopathy of prematurity screening in underserved Lipponcott Williams& Williams; 2005, pp. 359–64. areas in India using wide-field imaging, tele-medicine, L,18. Gopal Sharma T, Shanmugam M, Badrinath SS, Sharma A, non-physician graders and smart phone reporting. Indian J Agraharam SG, Choudhary A. Surgery for stage 5 retinopathy of Ophthalmol. 2014;62(1):41–9. prematurity: the learning curve and evolving technique. Indian 7. Cryotherapy for retinopathy of prematurity cooperative J Ophthalmol. 2000;48(2):101–6. group. Multicentric trial of retinopathy of prematurity: 3 19. Tasman W, Borrone RN, Bolling J. Open sky vitrectomy for months outcome. Arch Ophthalmol. 1990;108:195–204. total retinal detachment in retinopathy of prematurity. 8. Early Treatment of Retinopathy of Prematurity Cooperative Ophthalmology. 1987;94(4):449–52. Group. Revised indications for treatment of retinopathy of

How to cite this article Parveen S, Chetan R, Nishant B. Retinopathy of Prematurity: An Update, Sci J Med & Vis Res Foun 2015;XXXIII:93–96.

96 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

Current Role of Photodynamic Therapy in Ophthalmic Practice

Pukhraj Rishi and Vishvesh Agarwal

Shri Bhagwan Mahavir Introduction The PDT use in myopic CNV was established by Vitreoretinal Services, Photodynamic therapy (PDT) is a form of light- the results of the VIP reports 1 and 2 where reduc- Sankara Nethralaya, therapy using light-sensitive compounds that tion in BCVA was less with PDT as compared to 18 College Road, Chennai 600006, when exposed to light selectively become toxic to placebo (36% patients lost at least eight EDTRS 1 India targeted cells (phototoxicity). Most PDT applica- letters as compared to 51% with placebo) while tions involve three components: a photosensitizer, more number of patients had improvement in a light source and tissue oxygen. The combination BCVA (improvement in BCVA of at least five Correspondence to: of these three components leads to chemical ETDRS letters was seen in 40% with PDT as com- Pukhraj Rishi, destruction of tissues which have taken-up the pared to 13% with placebo) at 24-month Senior Consultant, photosensitizer and have been locally exposed to follow-up.8,9 Currently, PDT is recommended for Shri Bhagwan Mahavir Vitreoretinal Services, light of appropriate wavelength to produce react- use in myopic CNV in cases where anti-VEGF has 10 Sankara Nethralaya. ive oxygen species (ROS). These ROS are free radi- been ineffective or is contraindicated. E-mail: [email protected] cals (Type I PDT) generated through electron In patients with CNV due to angioid streaks, abstraction or transfer from a substrate molecule stability in BCVA is achieved with the use of and highly reactive state of oxygen known as PDT.11 However, the success rate achieved with singlet oxygen (Type II PDT). It is important to anti-VEGF in angioid streaks by Browning et al. distinguish PDT from other light-based and laser tilted the balance towards anti-VEGF as the pre- therapies such as laser wound healing and reju- ferred modality of treatment.12 PDT has also been venation, or intense pulsed light hair removal, used with some success in cases of inflammatory which do not require a photosensitizer. PDT is CNV due to multifocal choroiditis, punctate inner used clinically to treat a wide range of medical choroidopathy (PIC) and toxoplasmosis.13 conditions.2 The era of PDT in Ophthalmology Polypoidal choroidal vasculopathy (PCV) is a was initiated by results of the TAP study.3 The disorder characterized by subretinal polypoidal first indication for which PDT was approved in vascular lesions. PDT was found to be successful ophthalmology was choroidal neovascularization in improving BCVA in 56% cases and maintaining (CNV) in patients with age-related macular degen- vision in 31% cases of PCV.14 Currently, PDT is eration (AMD). recommended for treatment of juxtafoveal and The technique of administering PDT requires subfoveal PCV, alone or in combination with the combination of laser and photosensitizer intravitreal Ranibizumab (0.5 mg/0.1 ml).15 Visudyne®. PDT utilizes photosensitizer Visudyne® Central serous chorioretinopathy (CSCR) is a [liposomal benzoporphyrin derivative monoacid disorder characterized by pigmentary epithelial ring A (BPDMA)] given via intravenous infusion detachment with subretinal fluid. The use of PDT at a dose of 6 mg/m2 of body surface area. Fifteen is based on the rationale that primary choroidal minutes after the infusion, the ‘standard’ protocol hyperpermeability is the basic cause of CSCR. of focal light (light dose of 50 J/cm2, irradiance of Treatment with PDT leads to visual improvement 600 mW/cm2 of 689 nm light over 83 seconds) is of ≥2 lines in 43% cases while loss of ≥2 lines of delivered. This treatment is ‘selective’ in that the BCVA occurs in about 7.5%. cases. RPE atrophy photosensitizer is selectively taken up by the pro- seen in about 4% cases.16 liferating endothelial cells of the neovascular Apart from retinal lesions, various ocular tissue thus leading to occlusion and reducing col- tumors have been treated with PDT with variable lateral damage. PDT was first recommended for success rates. PDT is the one of the treatment cases of subfoveal classic or occult CNV in AMD.5 alternatives in recurrent choroidal melanoma.17 The approval of intravitreal Ranibizumab for PDT is also a good option for treatment of symp- treatment of CNV in AMD has led to decline in tomatic choroidal nevi, especially in cases with the use of PDT. The main advantage of anti-VEGF subretinal fluid. However, despite resolution of when compared with PDT is more improvement in subretinal fluid, it does not provide good local BCVA (77% vs 28%) and less reduction in BCVA tumor control.18,19 (21% vs 60%) at 2-year follow-up.6 PDT is cur- The use of PDT in patients with retinal capil- rently recommended for CNV in AMD either lary hemangioblastomas achieves regression of the refractory to anti-VEGF therapy or as monother- tumor, resolution of macular edema. However, apy in patients with contraindications for improvement in BCVA is not always seen (around anti-VEGF therapy.7 50% cases).20,21 On the contrary, the use of PDT

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 97 Recent advances

in choroidal hemangioma achieves excellent 2. Diamond I, Granelli SG, McDonagh AF, Nielsen S, Wilson CB, tumor control, resolution of macular edema as Jaenicke R. Photodynamic therapy of malignant tumours. 2 – well as exudative macular detachment along with Lancet. 1972; :1175 7. 3. Treatment of age-related macular degeneration with improvement in BCVA. This has made PDT as the photodynamic therapy (TAP) study group. Photodynamic preferred treatment option for cases of choroidal therapy of subfoveal choroidal neovascularization in age-related 22,23 hemangioma. There are a number of other macular degeneration with Verteporfin. Arch Ophthalmol. ocular tumors such as vasoproliferative tumors of 1999;117:1329–45. the retina, choroidal osteoma, retinal astrocytoma 4. van den Bergh H. Photodynamic therapy of age-related where PDT has been used with variable success macular degeneration: history and principles. Sem Ophthalmol. 16 – rates.24–26 2001; :181 200. 5. Verteporfin in Photodynamic Therapy Study Group. Ocular surface squamous neoplasia (OSSN) is Verteporfin therapy of subfoveal choroidal neovascularization in an ocular condition characterized by growth of age-related macular degeneration: two-year results of a neovascular tissue on the surface of the cornea randomized clinical trial including lesions with occult with no and sclera. PDT was first used for treatment of classic choroidal neovascularization—verteporfinin OSSN by Barbazetto et al. This led to its use for photodynamic therapy report 2. Am J Ophthalmol. 131 – treating OSSN, without extensive invasion, which 2001; :541 60. 6. Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, IanchulevT; is its current indication.27,28 ANCHOR Study Group. Ranibizumab versus verteporfin With the growing evidence in support of PDT photodynamic therapy for neovascular age-related macular for successful treatment of various retinal neovas- degeneration: two-year results of the ANCHOR study. cular lesions, the use of PDT in corneal neovascu- Ophthalmology. 2009;116(5):57–65. larization for prevention of corneal graft rejection 7. Schmidt-Erfurth U, Chong V, Loewenstein A, Larsen M, was explored. PDT achieves an immediate reduc- Souied E, Schlingemann R, Eldem B, Monés J, Richard G, tion in corneal neovascularization with decreased Bandello F. Guidelines for the management of neovascular age-related macular degeneration by the European Society of neovascularization maintained in 75% and com- Retina Specialists (EURETINA). Br J Ophthalmol. plete vascular occlusion achieved in 50% of 2014;98:1144–67. treated eyes at 1-year follow-up. Recently, PDT 8. Verteporfin in Photodynamic Therapy (VIP) Study Group. has also been used in combination with subcon- Photodynamic therapy of subfoveal choroidal junctival Bevacizumab for the treatment of neovascularization in pathologic myopia with verteporfin: corneal neovascularization. A triple combination 1-year results of a randomized clinical trial—VIP report 1. Ophthalmology. 2001;108:841–52. of PDT, subconjunctival Bevacizumab and topical Blinder KJ, 29–31 9. Blumenkranz MS, Bressler NM, Bressler SB, cyclosporine has also been tried. Donato G, Lewis H, Lim JI, Menchini U, Miller JW, Mones JM, However, with the growing utility of PDT in Potter MJ, Pournaras C, Reaves A, Rosenfeld P, Schachat AP, ocular conditions, its side-effects warrant consid- Schmidt-Erfurth U, Sickenberg M, Singerman LJ, Slakter JS, eration, too. The most common systemic side- Strong HA, Virgili G, Williams GA . Verteporfin therapy of effects encountered are infusion-related back pain subfoveal choroidal neovascularization in pathologic myopia: and minor allergic reactions at the injection site. 2-year results of a randomized clinical trial-VIP report no. 3. Ophthalmology. 2003;110:667–73. Cases of serious allergic reactions are extremely 10. Wong TY, Ohno-Matsui K, Leveziel N, Holz FG, Lai TY, Yu HG, rare though. Sunlight exposure is to be avoided Lanzetta P, Chen Y, Tufail A. Myopic choroidal for 3 days following PDT to avoid sunburn. The neovascularisation: current concepts and update on clinical most important ocular side effects are secondary management. Br J Ophthalmol. 2014;1–8. CNV, persistent choriocapillaris hyoperfusion and 11. Browning AC1, Chung AK, Ghanchi F, Harding SP, Musadiq M, pigmentary changes in the RPE in the treated Talks SJ, Yang YC, Amoaku WM; United Kingdom PDT Users fi area.32 All these concerns have led to the explor- Group. Vertepor n photodynamic therapy of choroidal fl neovascularization in angioid streaks: one-year results of a ation of reduced uence PDT (irradiance of prospective case series. Ophthalmology. 2005;112:1227–31. 2 2 300 mW/cm instead of 600 mW/cm ) by some 12. Neri P, Salvolini S, Mariotti C, Mercanti L, Celani S, authors with success rates similar to those Giovannini A. Long-term control of choroidal achieved with standard fluence. A novel approach neovascularisation secondary to angioid streaks treated with has been reducing the dose of verteporfinfrom intravitreal bevacizumab (Avastin). Br J Ophthalmol. 6 to 3 mg/m2. This modification has achieved 2009;93:155–8. Ruiz-Moreno JM, success rates similar to the standard fluence PDT 13. Montero JA, Arias L, Sanabria MR, Coco R, Silva R, Araiz J, Gomez-Ulla F, Garcia-Layana A. Photodynamic but with the theoretical advantage of reduced therapy in subfoveal and juxtafoveal idiopathic and 33–35 scarring. postinflammatory choroidal neovascularization. Acta In conclusion, indications of PDT extend from Ophthalmol Scand. 2006;84(6);743–48. ocular surface conditions to intraocular tumors, 14. Spaide RF1, Donsoff I, Lam DL, Yannuzzi LA, Jampol LM, making it a useful tool in the armamentarium of Slakter J, Sorenson J, Freund KB. Treatment of polypoidal the ophthalmologist. choroidal vasculopathy with photodynamic therapy. Retina. 2002;22:529–35. 15. Koh A1, Lee WK, Chen LJ, Chen SJ, Hashad Y, Kim H, Lai TY, References Pilz S, Ruamviboonsuk P, Tokaji E, Weisberger A, Lim TH. . fi fi 1. Moan J, Peng Q. An outline of the hundred-year history of PDT. EVEREST study: ef cacy and safety of vertepor n Anticancer Res. 2003; 23(5A):3591–600. photodynamic therapy in combination with ranibizumab or

98 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

alone versus ranibizumab monotherapy in patients with 26. Blasi MA, Scupola A, Tiberti AC, Sasso P, Balestrazzi E. symptomatic macular polypoidal choroidal vasculopathy. Photodynamic therapy for vasoproliferative retinal tumors. Retina. 2012;32:1453–64. Retina. 2006;26:404–9. 16. Lim JI, Glassman AR, Aiello LP, Chakravarthy U, Flaxel CJ, 27. Cekic O, Bardak Y, Kapucuoglu N. Photodynamic therapy for Spaide RF. Macula Society CSC Collaborative Study Group, conjunctival ocular surface squamous neoplasia. J Ocular Research and Education Committee and Website Committee. Pharmacol Therapeutics. 2011;27(2):205–7. Collaborative retrospective macula society study of 28. Barbazetto IA, Lee TC, Abramson DH. Treatment of conjuntival photodynamic therapy for chronic central serous squamous cell carcinoma with photodynamic therapy. Am J chorioretinopathy. Ophthalmology. 2014;121(5):1073–8. Ophthalmol. 2004;138:183–9. 17. Canal-Fontcuberta I, Salomão DR, Robertson D, Cantrill HL, 29. You IC, Im SK, Lee SH, Yoon KC. Photodynamic therapy with Koozekanani D, Rath PP, et al Clinical and histopathologic verteporfin combined with subconjunctival injection of findings after photodynamic therapy of choroidal melanoma. bevacizumab for corneal neovascularization. Cornea. 2011;30 Retina. 2012;32:942–948. (1):30–3. 18. García-Arumí J, Amselem L, Gunduz K, Badal J, Adan A, 30. Yoon KC, You IC, Kang IS, Im SK, Ahn JK, Park YG, Ahn KY. Zapata MA, Valldeperas X, Huste F, Corcóstegui B. Photodynamic therapy with verteporfin for corneal Photodynamic therapy for symptomatic subretinal fluid related neovascularization. Am J Ophthalmol. 2007;144(3):390–5. to choroidal nevus. Retina. 2012;32(5):936–41. 31. Kirat O, Al-Dhibi HA. Regression of aggressive corneal 19. Rundle P, Rennie I. Management of symptomatic choroidal vascularization after photodynamic therapy, subconjunctival naevi with photodynamic therapy. Eye (Lond). Avastin injections and topical cyclosporin-A 1% drops: a case 2007;21:1531–1533. report. Saudi J Ophthalmol. 2010; 24:151–4. 20. Papastefanou VP, Pilli S, Stinghe A, Lotery AJ, Cohen VML. 32. Wormald R, Evans JR, Smeeth LL, Henshaw KS. Photodynamic Photodynamic therapy for retinal capillary hemangioma. Eye therapy for neovascular age-related macular degeneration. (Lond). 2013;27:438–442. Analysis 1.13. Comparison 1 photodynamic therapy with 21. Sachdeva R, Dadgostar H, Kaiser PK, Sears JE, Singh AD. verteporfin versus placebo, outcome. Cochrane Rev. Verteporfin photodynamic therapy of six eyes with retinal 2009;4:45–46. capillary hemangioma. Acta Ophthalmol. 2010;88(8):334–40. 33. Reibaldi M, Cardascia N, Longo A, Furino C, Avitabile T, Faro S, 22. Singh AD, Kaiser PK, Sears JE, Gupta M, Rundle PA, Rennie IG. Sanfilippo M, Russo A, Uva MG, Munno F, Cannemi V, Photodynamic therapy of circumscribed choroidal Zagari M, Boscia F. Standard-fluence versus low-fluence haemangioma. Br J Ophthalmol. 2004;88:1414–18. photodynamic therapy in chronic central serous 23. Porrini G, Giovannini A, Amato G, Ioni A, Pantanetti M. chorioretinopathy: a nonrandomized clinical trial. Am J Photodynamic therapy of circumscribed choroidal hemangioma. Ophthalmol. 2010;149(2):307–15. Ophthalmology.2003;110(4):674–80. 34. Lai TY, Chan WM, Li H, Lai RY, Liu DT, Lam DS. Safety 24. Eskelin S, Tommila P, Palosaari T, Kivelä T. Photodynamic enhanced photodynamic therapy with half dose verteporfin for therapy with verteporfin to induce regression of aggressive chronic central serous chorioretinopathy: a short term pilot retinal astrocytomas. Acta Ophthalmol. 2008;86(7):794–9. study. Br J Ophthalmol. 2006;90:869–74. 25. Shields CL, Materin MA, Mehta S, Foxman BT, Shields JA. 35. Koytak A, Erol K, Coskun E, Asik N, Öztürk H, Özertürk Y. Regression of extrafoveal choroidal osteoma following Fluorescein angiography-guided photodynamic therapy with photodynamic therapy. Acta Ophthalmologica . half-dose verteporfin for chronic central serous 2008;1:135–137. chorioretinopathy. Retina. 2010;30(10):1698–703.

How to cite this article Rishi P, Agarwal V. Current Role of Photodynamic Therapy in Ophthalmic Practice, Sci J Med & Vis Res Foun 2015;XXXIII:97–99.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 99 Recent advances

Techniques of Fundus Imaging

Amit B. Jain, Vadivelu Jaya Prakash and Muna Bhende

Shri Bhagwan Mahavir Introduction Discussion in this review will be limited to Vitreoretinal Services, Ophthalmology is a specialized field of medicine, non-contrast techniques of fundus imaging along Sankara Nethralaya where we can directly visualize the pathology and with recent advances. A detailed discussion on treat accordingly. Imaging of fundus helps in doc- FFA and ICG is beyond the scope of this review. Correspondence to: umenting the disease process which further helps The list of available machines mentioned is by no Vadivelu Jaya Prakash in classifying, treating and following up effect- means exhaustive and does not indicate any com- Associate Consultant, ively. Fundus imaging helps in diagnosing various mercial interest of the authors. Shri Bhagwan Mahavir ocular and systemic disorders like diabetic retino- Vitreoretinal Services, pathy, hypertensive retinopathy, age-related Red free fundus photography Sankara Nethralaya macular degeneration, glaucoma, subacute bacter- Email: [email protected] It is a technique of monochromatic retinal ial endocarditis, leukemia, systemic malignancy imaging which uses green contrast filters to with ocular metastasis etc. and thus helps in modify individual tones in monochrome images effectively managing the condition. This review and the increased scattering of light at shorter focuses on various fundus imaging modalities wavelengths. Various fundus structures can be fl such as digital fundus photography, auto uores- better visualized by limiting the spectral range of fl 3 cence, infrared re ectance, etc. making a note of the illuminating source. recent advances in fundus imaging technology. Green light enables excellent contrast and view The history of fundus imaging dates back to early of fundus as the peak spectral sensitivity of the 20th century, but it has advanced as time has pro- human eye falls in the green–yellow portion of gressed. With the advent of digital imaging, the the spectrum. Less scatter compared to shorter fi lm-based imaging is almost an obsolete tech- wavelengths, results in a better view even in nique now. Table 1 summarizes the major differ- media opacities. Retinal vasculature and nerve fi ences in lm-based and digital imaging. fiber layer (RNFL) are best seen in red free photo- fi Fundus imaging can be de ned as a two- graphy, thus helping in better identification of dimensional image of a three-dimensional retinal hemorrhages, drusen, microaneurysms, RNFL fl tissue captured using re ected light. Fundus defects and exudates. For this reason, green filter imaging can be categorized into contrast and non- ‘red-free’ photos are routinely taken as baseline contrast modalities as shown in Table 2. images before fluorescein angiography.4

Table 1 Comparison of digital fundus and film-based fundus imaging1 Digital Film-based

Resolution 1000 pixels 10000 pixels (in ideal conditions) Stereoscopic viewing Available Available Image manipulation Easy Difficult Processing and duplication time Seconds Hours Lesion measurement Irregular tracing made easy Best fit circles Transmission Worldwide via internet (instantaneous) Manual delivery of copies (slow) Cost Installation cost high Installation cost less

Table 2 Various imaging modalities based on use of contrast Contrast Non-contrast

Fluorescein angiography (FFA) 1. Red-free photography Indocyanine angiography (ICG) 2. Color fundus photography a Stereo fundus photography b Digital fundus photography c Confocal scanning laser ophthalmoscopy (cSLO) 3. Fundus autofluorescence 4. Infrared reflectance 5. Hyperspectral retinal imaging 6. Adaptive optics SLO

100 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

Color fundus imaging A. Stereo-imaging Diagnostic information can be greatly improved by creating a visual sense of depth by laterally shifting the fundus camera a few millimeters between sequential photographs. The illuminating beam of the fundus camera falls on opposite slopes of the cornea creating a cornea-induced parallax.4 This results in pseudo three-dimensional image formation from an ordinary two- dimensional fundus photographs. Dedicated stereo display software is available for accurate align- ment of digital stereo images.4

B. Digital fundus photography Figure 2. Montage of FFA of the right eye of a Carl Zeiss Company in 1926 introduced the first patient with vasculitis showing commercially available fundus camera which pro- neovascularisation at the disc along with vided a 20° field of view of the retina.5 extensive capillary nonperfusion areas and laser Traditionally used fundus cameras (Fig. 1) provide marks superiorly. Note the enlarged view 30° to 45° field of view which can subsequently obtained by montage technique (approximately be increased by mosaic or montage patterns. 75°). Imaging beyond 50° is called wide-field pho- tography and the recent development came with C. Confocal scanning laser ophthalmoscopy imaging the introduction of ‘ultrawidefield’ photography. Some of the newer imaging techniques use the These include the Pomerantzeff camera,6 the principle of confocal scanning laser ophthalmos- Retcam (Clarity Medical Systems, Inc., Pleasanton, copy (cSLO). Instead of a bright flash of white CA, USA), the Panoret-1000™ camera (Medibell light as in traditional photography, cSLO uses Medical Vision Technologies, Haifa, Israel), the laser light to illuminate the retina. Confocal Optos® camera (Optos PLC, Dunfermline, UK), and imaging acts by a detailed point-by-point scan- the Staurenghi lens7 (Ocular Staurenghi 230 SLO ning of the entire field by a focused laser beam Retina Lens; Ocular Instruments Inc, Bellevue, and then capturing the reflected light through a WA, USA) etc. allowing 100° to 200° view of small confocal pinhole, which in turn suppresses fundus. This allows for simultaneous evaluation of any scattered or reflected light outside the focal the peripheral and central retina without causing plane that could blur the image. This result in a any patient discomfort. sharp, high-contrast image of an object layer located within the focal plane.8,9 The advantages of using cSLO over traditional fundus photography include improved image quality, suppression of scattered light, and patient comfort through less bright light, three- dimensional imaging capability, video capability, and effective imaging of patients who do not dilate well. Examples of cSLO-based ultrawidefield imaging (UWFI) systems include the Optos® camera (Optos PLC, Dunfermline, UK), and Spectralis® (Heidelberg Retina Angiograph (HRA 2), Heidelberg Engineering, Germany). The main limitation in wide-field imaging is the difficulty in projecting a curved surface on a flat two-dimensional plane (Greenland effect) and software are being developed to address this. Research is also going on to determine whether retinal surface area can be precisely measured in Figure 1. Zeiss FF 450 plus IR colour fundus square millimeters.10 camera which provides good quality colour fundus images with optical zoom of three magnification levels (20°, 30° and 50°) and FFA Fundus autofluorescence along with the option of adding ICG and FAF to Fluorescein angiography uses fluorescein dye to its software. delineate retinal vascular and associated

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 101 Recent advances

pathology, the basic nature of dye to cause fluor- are longer than the other colored wavelengths of escence helps in the diagnostic ability. The human the visible spectrum making them less prone to eye itself has few components which fluoresce absorption by blood and melanin. This results in without any external addition of dye. Imaging of greater amount of light (reflectance) being avail- such auto-fluorescing substances has given an able to form an image as compared to shorter altogether new dimension to diagnostic imaging. wavelengths in the visible spectrum, and hence Fundus autofluorescence imaging takes advantage constitute better tool for imaging structures of the intrinsic autofluorescence of lipofuscin, deeper to the RPE.18,19 normally found in RPE cells accumulated as a IR is a non-invasive en face imaging technique result of phagocytosis of the constantly shed which helps in visualizing sub-retinal pathology.18 photoreceptor outer segments. RPE dysfunction IR imaging has several advantages over flash leads to an imbalance between lipofuscin forma- fundus photography. The invisibility of infrared tion and clearance resulting in excessive accumu- light makes it better acceptable for imaging chil- lation of lipofuscin.11 Higher the lipofuscin dren and light-sensitive patients. As the penetra- content of the RPE cell, the more autofluorescent tion of infrared light is better, it acts as a useful it will appear on FAF. Atrophic (dead) RPE cells imaging tool in patient with media opacities like appear severely hypoautofluorescent as they do dense cataract. IR imaging may offer better visual- not contain lipofuscin, whereas viable cells have a ization of epiretinal membranes, cystoid macular varying content of lipofuscin and accordingly, a edema and deeper structures compared to fundus varying degree of hyperautofluorescence. photography and red-free imaging. IR was found Modified fundus cameras use a single flash to be superior to standard color fundus photog- with excitation spectrum of 535–585 nm to record raphy in screening for neovascular AMD.19 a single image whereas confocal-based systems use continuous scanning with an excitation spec- Hyperspectral retinal imaging trum of 488 nm resulting in recording of multiple It is a novel, non-invasive imaging technique for images with averaging to obtain a final image of ocular diagnosis using the spectroscopy principle high resolution. Overall image quality and contrast of retinal oximetry, which exploits the different are maximized with the cSLO’s multiple image spectral characteristics of oxygenated vs deoxyge- 12 acquisition and mean image calculation. nated hemoglobin to assess tissue perfusion. This FAF imaging gives information about the enables evaluation of functional characteristics of metabolic changes at the level of the RPE and tissue health. Its role is important in microvascular helps to identify areas that may be at high risk for disorders like diabetic retinopathy, sickle cell the development of geographic atrophy or CNV. disease, ARMD.20,21 FAF imaging has helped us with better under- standing of various diseases, classification, prog- Adaptive optics SLO nostication, and follow up in conditions like The optical properties of the normal eye result in a ARMD, CSR, Stargardt’s disease, Leber’s congeni- 11,13–17 point spread function width approximately the tal amaurosis and Serpiginous choroiditis. size of a photoreceptor. Standard fundus cameras have the shortcomings of inability to visualize Infrared reflectance individual cells/structure because of the various A newer variant of fundus photography, infrared aberrations of the visual system. Adaptive optics reflectance (IR) imaging uses infrared light instead uses mechanically activated mirrors to correct the of white light for illumination. Red wavelengths wavefront aberrations of the light reflected from

Figure 3. Left eye fundus photograph of 30 year old man with retinitis pigmentosa showing extensive bony spicules reaching almost upto the macula along with some atrophic changes. FAF image of the same eye clearly showing the demarcation between the viable (normal autofluorescence) and the atrophic areas (hypoautofluorescence).

102 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances the retina and thus allows individual photorecep- retinal view before taking the image, due to the tors to be imaged.22 Recent studies have shown ellipsoid mirror used for focusing the confocal the ability of adaptive optics-based system to ophthalmoscope. Even though it provides a very image microscopic blood vessels and the cone wide field of view, it is still unable to view the photoreceptor mosaic. Its utility has been shown entire retina in one shot and is prone to miss the in identifying reduced cone photoreceptors in anterior retinal findings. The extent of imaging of Retinitis pigmentosa.23 the superior and inferior peripheral retina is less Three commercially available machines which as compared to nasal and temporal periphery.35 incorporate some of the above recent imaging Also, there is a significant distortion and modalities are discussed further. decreased resolution of the extreme temporal and nasal peripheral retina.29 A method for correcting Optos® this peripheral distortion, when evaluating the The first and one of the most widely used com- retinal area and making measurements, has been 29 mercially available ultra-widefield systems is the described. Artifacts related to structures anterior Optos noncontact camera. The Optos system uti- to retina like eyelashes, implanted intraocular lizes an ellipsoid mirror to produce images with lens, vitreous opacities are known to occur in approximately 200° field of view, providing an Optos causing degradation of the quality and 36 image of more than 80% of the retina in a single extent of imaging. capture.24 The Optos provides various high- resolution imaging systems with multiple software Spectralis options catering to specific requirements. Also Heidelberg Spectralis (Fig. 2) has enhanced the instead of white light, Optos incorporates low role of fundus imaging by combining the spectral powered laser wavelengths that scan simultan- domain OCT with confocal SLO resulting in eously. This allows viewing of the retinal sub- enhanced anatomical details, improved reproduci- structures in their individual laser separations. The bility and automatic rescan at same site at red free view scans the sensory retina up to the follow-up. Simultaneous multimodal imaging pigment epithelial layer whereas the choroidal (Fig. 3) with FAF, infrared reflectance, FFA and 25 view scans layers from the RPE to the choroid. ICG is also possible. Previously, the Heidelberg Optos also provides ultra-widefield, high- Spectralis® provided a 25° and 35° field of view of resolution angiography, enabling a simultaneous the retina, with the possibility of a 55° noncontact central and peripheral view of the retina. Thus the lens attachment (HRA). A different model (HRA entire retinal vasculature can be imaged during +OCT) combines the features of HRA with spectral the dye transit. This is particularly useful in con- domain OCT and EDI OCT, thus providing an effi- ditions affecting periphery first like retinal vascu- cient tool for multimodal imaging of fundus. litis. Recent studies also support the added More recently, Heidelberg Engineering advantage of peripheral imaging in diabetic retin- (Heidelberg, Germany) has developed a noncon- opathy, vascular occlusion, choroidal mass, tact ultra-widefield angiography module for the Uveitis, choroidal dystrophies, retinal detachment, Spectralis® and Heidelberg Retina Angiograph pediatric retinal conditions and many more dis- (HRA 2) with 105° field of view.37,38 Even though orders.26–34 Wessel et al.26 reported that UWFI visualizes 3.2 times more retinal surface area than the conventional seven standard fields. Also in 10% of eyes, UWFI diagnosed peripheral retinal pathology not seen on traditional fundus imaging.26 Optos has wide range of ultra widefield devices depending upon the various features it provides. While the Optos 200Dx and Optos 200C provides features like color fundus photography, ophthalmoscopy along with red free and choroidal imaging, Optos Daytona has the added feature of FAF. Optos 200Tx goes further with the addition of FFA and the newly introduced Optos California includes ICG in addition to the all above- mentioned features thus making it feasible for ultrawidefield multimodal imaging.25 Despite its ability to produce dynamic widefield fundus images, the Optos Optomap® has several limitations. It requires a skilled technician to Figure 4. Spectralis by Heidelberg Engineering obtain peripheral images. Also unlike traditional showing simultaneous FFA and ICG (multimodal fundus photography, Optos does not allow a imaging).

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 103 Recent advances

the field of view is less when compared to Optos, are found to be better and more informative than on qualitative analysis, the high-contrast, undis- that taken by Optos.24 Also image capturing is torted and evenly illuminated images of Spectralis easy in Spectralis because of the use of infrared

Figure 5. Spectralis widefield ICG imaging done by a 150 degree non contact lens system shows a network of polypoidal vessels (arrow heads) suggestive of IPCV. The late phase of ICG shows multiple choroidal folds (black arrows) in periphery that could have been missed on a routine ICG.

Figure 6. Multimodal imaging of a patient with Left eye CNVM done on Spectralis. A. FAF shows presence of hypoautofluorescent centre surrounded by a hyperautofluorescent margins. B. Infrared reflectance shows an isoautofluorescent centre with hyperautofluorescent margins. C. Late phase of FFA shows staining at the centre along with leakage at the margins suggestive of active neovascular membrane which can be appreciated as a distinct, well demarcated membrane on ICG (D). Spectral domain OCT (E) shows dense subretinal fibrin deposition with irregular RPE Bruch complex. Note presence of subretinal fluid and cystoid spaces suggestive of activity.

104 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances light for focusing the confocal ophthalmoscope (instead of ellipsoid mirror as in Optos), one can view the retina before taking an image.39 In add- ition, Staurenghi contact lens can be used in con- junction with the Spectralis® to provide up to 150° field of view in a single shot.7,39 A recent study has shown utility of Spectralis in imaging infant fundus along with FFA to look for any retinal dis- eases.40 One limitation of Spectralis is that instead of true color images, pseudo color images are dis- played, which may not represent the exact clinical picture.

RetCam Figure 8. RETCAM image of right eye of a child RetCam is an advanced, wide-field digital imaging showing Intraocular Retinoblastoma undergoing system which provides good quality of ophthalmic treatment. Note the active tumour involving fi visualization and photo documentation with great macula with calci cation and another regressing ease. It has been found to be an effective tool for tumour nasally with surrounding chorioretinal fi fl immediate evaluation of pediatric ocular path- atrophy and central sh esh appearance. ology. The newer-generation RetCam 3 provides RETCAM helps in documenting the treatment further high-resolution digital images and can be response by serial imaging. shared electronically with an ophthalmologist or a physician and can be tracked longitudinally over time. RetCam 3 is equipped with a family of inter- changeable lenses that provides a wide range of image options allowing the physician to view both anterior and posterior ocular pathology.41,42 Retcam-3 has five changeable lenses: 130° (pedi- atric retina and adult anterior chamber), 120° (pediatric and young adult), 80°(high contrast pediatric and adult), 30° (high magnification) and Portrait (external imaging).43 The major use of RetCam has been in screening, classification and follow-up of pediatric conditions like retinopathy of prematurity (ROP) (Fig. 7), Retinoblastoma (Fig. 8), Coats disease (Fig. 9) etc. It helps in iden- tifying the appropriate intraocular group of retino- Figure 9. RETCAM image of right eye of a young blastoma, assessing treatment response, regression boy showing bullous exudative retinal patterns and to detect any recurrence. It also detachment with presence of dense subretinal exudates and telangiectatic vessels confirming the diagnosis of Coats disease.

allows screening of premature infants at risk for ROP and has been shown to be an invaluable tool in resident training, parent education and photo documentation of ROP.44 RetCam 3 can also be equipped with an optical light source to perform fluorescein angiography which may be helpful in differentiating between diseases like Coats and Retinoblastoma. RetCam has gained great success as a screening imaging tool in various national and international tele-ophthalmology projects such as KIDROP (Karnataka Internet-Assisted Figure 7. RETCAM image of Lasered Stage 2 Diagnosis of Retinopathy of Prematurity), and Zone I ROP with plus disease—left eye showing SUNDROP (Stanford University Network for tortuous vessels at posterior pole. Note presence Diagnosis of Retinopathy of Prematurity).45,46 of ridge just temporal to macula and lasered RetCam in addition to fundus imaging can also be avascular zone anteriorly. used to image and document the angle and other

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 105 Recent advances

anterior segment abnormalities like iris nevus, 16. Burke TR, Duncker T, Woods RL, et al Quantitative fundus pigment dispersion/pseudoexfoliation, neovascu- autofluorescence in recessive Stargardt disease. Invest 55 – larization etc.43 Ophthalmol Vis Sci. 2014; (5):2841 52. 17. Vujosevic S, Vaclavik V, Bird AC, Leung I, Dandekar S, Peto T. Conclusion Combined grading for choroidal neovascularisation: colour, fluorescein angiography and autofluorescenceimages. Graefes Different retinal diseases require different imaging Arch Clin Exp Ophthalmol. 2007;245(10):1453–60. modalities for better understanding and manage- 18. Elsner AE, Burns SA, Weiter JJ, Delori FC. Infrared imaging of ment. The field of fundus imaging is developing sub-retinal structures in the human ocular fundus. Vision Res. rapidly and several new and exciting technologies 36:191–205. Miura M, are on the horizon which will cater to the needs of 19. Elsner AE, Beausencourt E, et al Grading of infrared confocal scanning laser tomography and video displays of an ophthalmologist. This will help us in evolving digitized color slides in exudative age-related macular our understanding of various disease entities thus degeneration. Retina. 22:300–8. helping us in better management of our patients. 20. Gao L, Smith RT, Tkaczyk TS. Snapshot hyperspectral retinal camera with the Image Mapping Spectrometer (IMS). Biomed References Opt Express. 2012;3(1):48–54. Kashani AH, 1. Yannuzzi LA, Ober MD, Slakter JS, et al Ophthalmic fundus 21. Lopez Jaime GR, Saati S, Martin G, Varma R, imaging: today and beyond. Am J Ophthalmol. Humayun MS. Noninvasive assessment of retinal vascular 2004;137:511–24. oxygen content among normal and diabetic human subjects: a 2. Abràmoff MD, Garvin MK, Sonka M. Retinal imaging and study using hyperspectral computed tomographic imaging 34 – image analysis. IEEE Trans Med Imaging. 2010;3:169–208. spectroscopy. Retina. 2014; (9):1854 60. Roorda A, 3. Behrendt T, Slipakoff E. Spectral reflectance photography. Int 22. Romero-Borja F, Donnelly W Iii, Queener H, Hebert T, Ophthalmol Clin. 1976;16:95–100. Campbell M. Adaptive optics scanning laser ophthalmoscopy. 10 – 4. Bennett TJ, Barry CJ. Ophthalmic imaging today: an Opt Express. 2002; (9):405 12 Tojo N, ophthalmic photographer’s viewpoint – a review. Clin Exp 23. Nakamura T, Fuchizawa C, Oiwake T, Hayashi A. Ophthalmol 2009;37:2–13. Adaptive optics fundus images of cone photoreceptors in the 5. Ciardella A, Brown D. Wide-field imaging. In: Agarwal A (ed.) macula of patients with retinitis pigmentosa. Clin Ophthalmol. 7 – Fundus Fluorescein and Indocyanine Green Angiography: A 2013; :203 10. Witmer MT, Textbook and Atlas. Thorofare: Slack Inc., 2007, pp. 79–84. 24. Parlitsis G, Patel S, Kiss S. Comparison of fi fl 6. Pomerantzeff O. Equator-plus camera. Invest Ophthalmol. ultra-wide eld uorescein angiography with the Heidelberg fi 1975;14(5):401–6. Spectralis(®) noncontact ultra-wide eld module versus the Optos 7 – 7. Staurenghi G, Viola F, Mainster MA, Graham RD, (®) Optomap(®).Clin Ophthalmol. 2013; :389 94 Harrington PG. Scanning laser ophthalmoscopy and 25. http://www.optos.com/en/Products/Retinal-imaging-products/ fi angiography with a wide-field contact lens system. Arch Ultra-wide eld-imaging (6 May 2015). Wessel MM, ’ Ophthalmol. 2005;123(2):244–52. 26. Aaker GD, Parlitsis G, Cho M, D amico DJ, Kiss S. fi 8. Woon WH, Fitzke FW, Bird AC, Marshall J. Confocal imaging of Ultra-wide- eld angiography improves the detection and fi 32 the fundus using a scanning laser ophthalmoscope. Br J classi cation of diabetic retinopathy. Retina. 2012; – Ophthalmol. 1992;76(8):470–4. (4):785 91. Wessel MM, 9. Castro Lima V, Rodrigues EB, Nunes RP, Sallum JF, Farah ME, 27. Nair N, Aaker GD, et al Peripheral retinal fi fl Meyer CH. Simultaneous confocal scanning laser ischaemia, as evaluated by ultra-wide eld uorescein ophthalmoscopy combined with high-resolution angiography, is associated with diabetic macular oedema. Br J 96 – spectral-domain optical coherence tomography: a review. J Ophthalmol. 2012; (5):694 8. Prasad PS, fi Ophthalmol. 2011;2011:743670. . 28. Oliver SC, Coffee RE, et al Ultra wide- eld 10. Croft DE, Van Hemert J, Wykoff CC, et al Precise montaging angiographic characteristics of branch retinal and hemicentral 117 – and metric quantification of retinal surface area from retinal vein occlusion. Ophthalmology. 2010; :780 4. Spaide RF. ultra-widefield fundus photography and fluorescein 29. Peripheral areas of nonperfusion in treated central fi fl angiography. Ophthalmic Surg Lasers Imaging Retina. retinal vein occlusion as imaged by wide- eld uorescein 31 – 2014;45:312–7. angiography. Retina. 2011; :829 37. Coffee RE, fi 11. Holz FG, Steinberg JS, Göbel A, Fleckenstein M, 30. Jain A, McCannel TA. Ultra wide- eld imaging of Schmitz-Valckenberg S. Fundus autofluorescence imaging in choroidal metastasis secondary to primary breast cancer. Semin 24 – dry AMD: 2014 Jules Gonin lecture of the Retina Research Ophthalmol. 2009; :34 6. Tsui I, Foundation. Graefes Arch Clin Exp Ophthalmol. 2015;253 31. Kaines A, Schwartz S. Patterns of periphlebitis in fi fl (1):7–16. intermediate uveitis using ultra wide eld uorescein 24 – 12. Park SP, Siringo FS, Pensec N, et al Comparison of fundus angiography. Semin Ophthalmol. 2009; :29 33. Kaines A, fi autofluorescence between fundus camera and confocal scanning 32. Tsui I, Sarraf D, et al The use of ultra wide eld fl laser ophthalmoscope-based systems. Ophthalmic Surg Lasers uorescein angiography in evaluation and management of 24 – Imaging Retina. 2013;44(6):536–43. uveitis. Semin Ophthalmol. 2009; :19 24. Anderson L, 13. Scholl HP, Chong NH, Robson AG, Holder GE, Moore AT, 33. Friberg TR, Singh J. Ultrawide-angle retinal Bird AC. Fundus autofluorescence in patients with leber imaging and retinal detachment. Semin Ophthalmol. 2007; 22 – congenital amaurosis. Invest Ophthalmol Vis Sci. 2004;45 :43 7. Fung TH, (8):2747–52. 34. Yusuf IH, Smith LM, Brett J, Weston L, Patel CK. fi fl 14. Malamos P, Masaoutis P, Georgalas I, et al The role of fundus Outpatient Ultra wide- eld intravenous fundus uorescein autofluorescence imaging in the study of the course of posterior angiography in infants using the OptosP200MA scanning 98 uveitis disorders. Biomed Res Int. 2015;2015:247469. . laser ophthalmoscope. Br J Ophthalmol. 2014; (3): – 15. Nam KT, Yun CM, Kim JT, et al Central serous 302 4. Bonnay G, chorioretinopathy fundus autofluorescence comparison with 35. Nguyen F, Meunier I, et al Screening for retinal fi two different confocal scanning laser ophthalmoscopes. Graefes detachment using wide-- eld retinal imaging. J Fr Ophtalmol. 34 – Arch Clin Exp Ophthalmol. 2015. [Epub ahead of print]. 2011; :482 5.

106 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Recent advances

36. Dunphy RW, Wentzolf JN, Subramanian M, et al Structural 42. http://www.claritymsi.com/international/retcam3.html as features anterior to the retina represented in panoramic accessed on 4 May 2015. scanning laser fundus images. Ophthalmic Surg Lasers Imaging. 43. http://www.claritymsi.com/us/downloads/Lenses&Images_2009_ 2008;39:160–3. f.pdf as accessed on 4 May 2015. 37. http://www.optech.net.au/optech_net005.htm as accessed on 4 44. Chiang M, Melia M, Buffenn AN. Detection of clinically May 2015. significant retinopathy of prematurity using wide-angle digital 38. http://www.heidelbergengineering.com/us/products/ retinal photography—a report by the American Academy of spectralis-models as accessed on 4 May 2015. Ophthalmology. Ophthalmology. 2012;119(6):1272–1280. 39. Witmer M, Kiss S. Wide-field imaging of the retina. Surv 45. Vinekar A, Gilbert C, Dogra M, et al The KIDROP model of Ophthalmol. 2013;58(2):143–54. combining strategies for providing retinopathy of prematurity 40. Fung TH, Yusuf IH, Xue K, et al Heidelberg spectralis screening in underserved areas in India using wide-field ultra-widefield fundus fluorescein angiography in infants. Am J imaging, tele-medicine, non-physician graders and smart phone Ophthalmol. 2015;159:78–84. reporting. Indian J Ophthalmol. 2014;62(1):41–9. 41. Linder BJ. The Value of RetCam system. http://www.claritymsi. 46. Wang SK, Callaway NF, Wallenstein MB, et al SUNDROP: six com/international/downloads/references/ years of screening for retinopathy of prematurity with TheValueofRetCam2011.pdf as accessed on 6 May 2015. telemedicine. Can J Ophthalmol. 2015;50(2):101–6.

How to cite this article Amit BJ, Jaya Prakash V, Muna B. Techniques of Fundus Imaging, Sci J Med & Vis Res Foun 2015;XXXIII:100–107.

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 107 Ophthalmic photography

Insight Ophthalmic Photography Competition

Jaydeep Avinash Walinjkar and Mohammadarif Mulla

Ophthalmic photography is an art in itself, with Category 4: Anterior segment slit lamp the skill of the photographer and the camera used photography being paramount in capturing the pathology in a Category 5: Ophthalmic Smartphone photography way that the picture conveys the message without Category 6: Ophthalmic external photography any words. The photographer is however almost always forgotten once the photograph is taken. Each participant was allowed to send a maximum of With a vast spectrum of clinical cases, Sankara 2 entries under each of the six categories. All the Nethralaya prides itself on having a very talented photographs received were compiled and segregated group of ophthalmic photographers as well as into their respective categories. They were judged by skilled amateurs. Together they contribute to an three external judges, all known for their interest in excellent documentation of disease conditions in ophthalmic imaging and photography. all fields of Ophthalmology. This issue of Insight Dr Mahesh P Shanmugam, Head, Vitreoretinal wishes to recognize their talent by publishing the and Ocular Oncology Services, Sankara Eye results of an in house ophthalmic photography Hospitals, Bangalore competition, open to all employees who can click a Dr Nitin Shetty, Director, The Retina Clinic, photograph (professionals as well as amateurs). Bangalore We received entries from 14 participants Dr Shobhit Chawla, Medical Director & Chief including professional ophthalmic photographers Vitreoretinal Surgeon, EYE Q-PNK Super Specialty as well as ophthalmologists for six categories. Eye Hospitals, Lucknow Winners were selected under each category. Category 1: Fundus photography (Single frame or Each category had 2 winners with the top two Montage): including colour, red free and scores (1st prize and 2nd prize). One photograph autofluorescence images with the highest individual score across all the six Category 2: Fundus fluorescein angiography categories was chosen for the “Best Photograph” Category 3: Indocyanine angiography award.

Category: Fundus Photo

Winner: Mr. Chidambaram K, Sankara Nethralaya, Chennai (employee number: 1100968)

108 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Ophthalmic photography

Second Prize: Mrs. Gouri Das, Sankara Nethralaya, Kolkata (employee number: 1102665 )

Second Prize: Mr. Shankar K, Sankara Nethralaya, Chennai (employee number: 1101881)

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 109 Ophthalmic photography

Category: Fundus Fluorescein Angiography

Winner: Thilak M, Sankara Nethralaya, Chennai (employee number: 1103580)

Second Prize: Mr. Chidambaram K, Sankara Nethralaya, Chennai (employee number: 1100968)

110 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Ophthalmic photography

Category: Indocyanine Green Angiography

Winner: Mr. Shankar K, Sankara Nethralaya, Chennai (employee number: 1101881)

Second Prize: Hariharan C. S, Second Prize: Thilak M, Sankara Nethralaya, Chennai Sankara Nethralaya, Chennai (employee number: 1103478) (Employee number: 1103580)

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 111 Ophthalmic photography

Category: Slitlamp Photography

Winner: Mr. Shankar K, Sankara Nethralaya, Chennai (employee number: 1101881)

Second Prize: Thilak M, Sankara Nethralaya, Chennai (Employee number: 1103580)

112 Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | Ophthalmic photography

Category: Smartphone Photography Category: External Photography

Winner: Mr. Stephen D (Employee number: 1101758)

Winner: Dr Shahid Alam M D (Employee number: 1101308)

Second prize: Dr Shahid Alam M D (Employee number: 1101308)

Second Prize: Mr. Shankar K, Second prize: Dr. R. Srikanth (Employee number: Sankara Nethralaya, Chennai 1103997) (employee number: 1101881)

Sci J Med & Vis Res Foun June 2015 | volume XXXIII | number 2 | 113 Developing Clinical Empathy: Enhancing Patients’ Satisfaction

Tarun Sharma

Director, Shri Bhagwan The practice of medicine is an art, not a trade; a calling, Mahavir Vitreoretinal not a business; a calling in which your heart will be Services, Sankara exercised equally with your head. Nethralaya A physician needs a clear head and a kind heart. Corresponding author. Tarun Sharma, Director, Shri Bhagwan Mahavir Vitreoretinal Services, tory unfolds… Sankara Nethralaya. S Email: [email protected] Many many years ago, a patient underwent a successful scleral buckling surgery; however, he developed buckle infection in the immediate postoperative period, leading to panophthalmitis and early orbital cellulitis. The eye could not be salvaged and had to be eviscerated as an emergency procedure at midnight.

The patient was relieved off the severe pain and the family went back.

Around 6 weeks later, the family returned with a gift for the doctor: a pair of trousers and a box of sweets with an invitation to visit his home whenever the doctor visits the city of joy, Kolkata!

The doctor was dumbfounded.

There he discovered how important the trust between a doctor and a patient is; and these gifts items were simply an expression of love and gratitude towards that TRUST.

Meet the living GOD, everyday…

Life is a journey: a journey of everyday learning; and for a doctor, it is a learning from every patient.

This is the kind of learning that text books and medical schools do not include in their curriculum, this is a learning that is not taught in residency, this is a learning that is not much discussed in scientific forums.

This is a LEARNING, we as doctors, EXPERIENCE with our patients, who are indeed living GOD, as was shared by the late Dr KP Misra, a well-known cardiologist of yesteryears, in one of his teachings.

Anyone who stops learning is old, whether at twenty or eighty. Anyone who keeps learning stays young. — Henry Ford Life is a journey, not a destination. Each day presents an opportunity for learning. Developing Clinical EMPATHY

Well, as we all know that the practice of medicine is an art and a science.

It is much harder to acquire the art than the science.

The science aspect we do learn in medical schools and/or during fellowships; but to learn the art, we need to develop sensitivity: we need to put ourselves in patients’ shoes.

Treat the patient, not just the disease; follow the patient-centered approach, and not just the disease-centered approach.

Remember that behind the retina, there is an individual; behind that individual, there is a family; behind that family, there is a neighborhood and extended family; behind the extended family, there is a network of humans, either physically or digitally and so on. Therefore, a doctor’s diagnostic skill to identify the disease or surgical skill to manage the disease is just not suffi- cient; what is needed is to communicate in layman terms the jargon of his diagnosis, treatment options, risks or benefits and so on. For the doctor, this might be a repetition or a routine, but for a patient, it is an experience. Even for a disease that has bad prognosis, the way the information is shared, the way the patients is educated, the way the body language is used, there is tremen- dous satisfaction not just for the patient and his family, but to the doctor as well. It is not just sharing of the information in a monotonous voice with a stone face or not answering his queries or his questions. It is to show an empathy, clinical empathy!

 It is to show that we are here to help you.  It is to show that we do understand their expectations.  It is to show that we do not dampen their hope, especially, in those challenging clinical settings wherein the outcome is rather extremely guarded.  It is to show that we have answered all their questions.  It is to show that we do encourage him to come back or write to us for any query they might have.  It is to show that our body language and voice and choice of words all are in unison.

Remember in any kind of communication there are 4 components: sender (we, the doctor), the message (verbal or written), the media (phone, e-mail, oral, Skype and so on), and the receiver (the patient). Which component is the most

important? Guess? QUIZ TIME!! A: The receiver, the patient the receiver, The A: What Vs How:

It is not what you communicate, but how you communicate: with or without that EMPATHY.

Our skill of clinical empathy would get sharpened as we practice it.

 It builds trust.  It strengthens one of the strongest doctor-patient relationships.  It sustains the great rapport between a doctor and a patient.  It brings back the hope and confidence in their minds.

Below are 10 Maxims that could be followed so as to nurture CLINICAL EMPATHY:

1. Greet the patient first and try to judge his anxiety toward his ailments or expectation after the treatment.

2. Evaluate how much he/she knows about the diagnose or treatment; add to his/her knowledge pool.

3. Share the treatment options; help a patient make the right choice or decision.

4. Use a simple drawing, clinical images or other tests as a tool to reinforce your verbal explanation.

5. As you enhance their knowledge of how the normal eye works, their understanding of the abnormality will also increase and they would be a great partner in their evaluation and treatment.

6. Do not lose your temper, if the same questions are being asked by him or family members repeatedly. And always end the consultation with a simple sentence: Is there any other question or query you have?

7. Do not blame the ‘other’ doctor for his present condition or his ill fate.

8. However , if all goes well: give the credit to him: ‘you are one of the luckiest patients of the day who has made such good visual recovery, much more than our expectations: Congratulations! I am very pleased. God is kind to both of us.’

9. W ords have power, healing power, use them to your advantage, use them to heal the wound and spirit.

10. Do not hesitate to put a hand on the shoulder; and silently make a prayer for his well-being. Last, but not least: go down memory lane and recall, when you did not know retinal surgery or when you were just learning, the patient also did not know about you and your skill but he sur- rendered himself to you. The learning we got from so many hundreds and thousands of patients is that there is no way we can say thank you to them; but now that your hands are stable, you are more mature, you can definitely hold those trembling hands.

Many a times we all like to emulate people and their lofty goals; however, only a few achieve them. Hence, it is good to know the barriers that hinders clinical empathy. There are three barriers:  Time Barriers: need to examine more and more patients; it adds to anxiety and a kind of psychological barrier.  Considering Empathy, not an important issue: focusing on just science, the treatment and surgery, just the disease leaving out the patient as a whole.  Negative emotions of physicians: when patients ask many questions or share the views of another doctor or not happy with the outcome.

Studies have shown that number one complaint patients have about their doctors is the perception that they simply don’t listen. Therefore, the first step towards learning is to become a GOOD Listener.

Did You know that there is as much Wisdom in listening, as there is in speaking?!!

So, enjoy the freedom & journey of learning to imbibe the great skill - CLINICAL EMPATHY - of becoming a great doctor.

Medicine is a calling, not a business.

A calling which exacts from you, at every turn, self-sacrifice, devotion, love, and tenderness to your fellow-men.Once you get down to a purely business level, your influence is gone and the true light of your life is dimmed. The physician’s work is not, and must not, always be financially rewarding.

REMEMBER: Work is our worship which we must do with three attributes: Sincerity, Dedication and utmost Love. List of fellows trained in Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya (1979–2013)

Dr M S Ravindra Dr Rajiv Mirchia Dr Debabrata Dutta Dr Seemant Raizada Dr Narinder K Lath Dr Shabhit Chawla Dr Alay Banker Dr Vinata Rajendran Dr Sitaramanjaneyalu B Dr Lalit Mohan Shukla Dr Monoj Govila Dr Joshua George Dr Vatsal S Parikh Dr Zia Ul Hasan Dr Rajani R Battu Dr Mahesh J Patel Dr Sunil N Parikh Dr Sanowar Hossain Dr Manju Kulkarni Dr SeetharamanJeneyulu Dr Partha Biswas Dr Candace Mary D’souza Dr Sridhar Rao B Dr Haresh Asnani Dr Vasanth N Patel Dr Amal Deb Dr Gooty Agraharam Satish Dr Sanjiv Hansraj Dr Malay Chaturvedi Dr Neeraj Sanduja Dr Prema Padmanabhan Dr Vinod Jain Dr Prashant Keshav Bhawankule Dr Ramesh Raghavendran Sivaraj Dr Madhav R Honnatti Dr Ravi Matani Dr Suresh Ramchandani Dr Satyen Deka Dr Hemanth Doshi Dr Gupta R P Dr Sheik Mehub Sobhan Dr Madhushudan Dr Ravishankar K V Dr Ajay Dudani Dr Mohammad Delwar Hossain Dr K Ravishankar Dr Challa J K Dr Devinder Singh Virdi Dr Parveen Kharbanda Dr Syed Gulam Ahmed Dr Nitin G Prabhu Desai Dr Rajat Agarwal Dr Mihika Sashital Dr Kohli C M Dr Niren R Dongre Dr Milan D Thakkar Dr Rajini Kantha Dr Murgesh Kanubhai Kotia Dr V K Dhull Dr Preetam Singh Dr Suhas Jijabrao Sonawane Dr Balasubramanian Dr D Ramamurthy Dr Anjali Nicholson Dr Vaidya Ashish Rabindra Dr Lingam Gopal Dr Sourav Sinha Dr Mehul C Shah Dr Agrwal Santosh Hanuman Dr Mythili Sriram Dr Rajasekar D Kotrappa Dr Raj Kumar Gupta Dr A Giridhar Dr Anand Subramanyam Dr Atul Ursekar Dr Shishir Narain Dr Cyrus Shroff Dr Surendra Basti Dr Saurabh Luthra Dr Madhivanan Natarajan Dr Malhar Soni Dr Buddi Rajiv Dr Salil Arab Mehta Dr Suman Dr Gargee Gupta Dr Dhanshree Arun Deshpande Dr Aruna Parekh Dr Pankaj Singhal Dr Premalatha Agarwal Dr Bhushan Uttam Khare Dr Jyotirmoy Biswas Dr Sanjeev Doshi Dr Sunil K Bhandari Dr Pathengay Avinash Dr Anil Kumar Sharma Dr Arun Elhence Dr Paritosh A Kamdar Dr Tapan Kumar Samanta Dr Nishikant Jaywant Borse Dr S Natarajan Dr Sanjay Srivastava Dr Prasan M Rao Dr Anil Verma Dr Shroff Rahul Ashok Dr Bikash Basu Dr Vinay Nangia Dr S A Md O S Kutubi Dr Gautam Panda Dr Preetam Manmohan Samant Dr Saraf P K Dr Upsham Goyal Dr Debashis Das Dr Hiren Saikia Dr Vipin Kumar VIG Dr Sandeep P Thakur Dr Jajneswar Bhunia Dr Anand Saxena Dr Kumar K S Dr Mahesh G Dr Tarun Sharma Dr Sangeet Mittal Dr Ekta Anand Dr Vinay Kumar Garg Dr Pramod S Bhende Dr Sunil Mehra Dr Ajeet Madhav Wagle Dr Brahma Reddy K Dr Gajendra Chawla Dr Ashwini C K Dr Surbhit Choudhry Dr Praveen R Murthy Dr Vimal Sarup Dr Shammi Kapoor Dr Sandeep K Saha Dr Ravi Krishna N Dr Tashwala J B Dr P Mahesh Shanmugam Dr Pratik Ranjan Sen Dr Ramesh K Dr Muna Ganesan Dr Randeep Sharma Dr Madhav Rao Dr Vijaya R Dr Puneet Gupta Dr Rajesh Gupta Dr Swati Agarwal Dr Bhatt N S Dr Mahesh Panwar Dr Surendra Shetty Dr Rajiv Raman Dr Sharad Rastogi Dr Sandip Mitra Dr Mufazzal I Dr Siddarthan V Dr Ashok Monga Dr Salil Gupta Dr Shobana Nair P K Dr Girish S Rao Dr Shah Nitant Arun Dr Sharma B P Dr Jaishankar Dr Tushar Kanti Sinha Dr Bhavsar Kaushal Bipinchandra Dr Deepak Khosla Dr Murlidhar S T Dr Prashant Saikia Dr Mohanned Nizammudin S H Dr Mohan Rajan Dr Roysarkar T K Dr Bibhuti Bhushan Dr Kasinathan Dr Lokesh Gupta Dr Naresh Yadav Dr Prathima Kathil Dr Rajiv Thakore Dr Pradip K Mohantha Dr Krishnamurthy Dr Ranjan Mukherjee Dr Ahmed S U Dr Nitin S Shitut Dr Hitendra Mehta Dr Manoj Bhatt Dr Radha Rani Sharma Dr Manoj Dr Padmaja Kumari Rani Dr Nitin S Shetty Dr Byanju R N Dr Karobi R Lahiri Dr Vinit Sah Dr Sumeet Chopra Dr Manisha Agarwal Dr Sunil Kumar Sah Dr Onik Moyong Dr Neelam Kumari Upadhyay Dr Girish A Gadre Dr Jayantha Chowdhry Dr Lalitendu Satpathy Dr Sandeep Vasudeo Mondkar Dr Rajeev K Reddy (Continued) List of fellows trained in Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya (1979–2013)

Dr Sribharghava Dr Radha R Das Dr Tandava Krishnan P Dr Bikramjit P Pal Dr Pooja Sinha Dr Ashish Rawal Dr Nishant Vijay Radke Dr Sagar S Bhuibhar Dr Vikas Khetan Dr Himanshu Deshmukh Dr Ramesh Venkatesh Dr Vishal Rameshkumar Raval Dr Debajit Deka Dr Shailaja S Dr Lala Akhundova Dr Lakshmi Kuniyal Dr Mahesh P Uparkar Dr Chinmay Prakash Nakhwa Dr Sachin B Kabre Dr Gullapalli V Ramkumar Dr Karthik R Meda Dr Arindam Roy Dr Amit Nagpal Dr Mahesh P Uparkar Dr Swapnesh Deepak Sawant Dr Chtralekha De Dr Sumita Sharma Dr Arun Bharghava Dr Parthopratim Dutta Majumder Dr Vijay Pratap Singh Tomar Dr Ramakant Kankara (Uvea & Medical retina) (Uvea & Medical retina) Dr Nishank Mittal Dr Sheena Liz Mani Dr Harshali Subhash Kamat Dr Ramesh N Patil Dr Somendra Pratap Chaudhary (Medical Retina) Dr Gaurav Mathur Dr Chetan Rao Dr Bhavin J Patel Dr Md Salman Md Saleh Kazi Dr Parag Chandrasekhar Apte Dr Swakshyar Saymya Pal Dr Alok Ashwinbhai Kathiara Dr Rekha S Dr S Pradeep Dr Hari Narayan Prasad Dr James Subratkumar Adams Dr Mansi Kishnani Dr Vasudev Chakravarty Dr Sanjiv Maru Dr Maneesh Dhupper Dr Eesh Nigam Dr Sriram Gopal Dr Atheeshwar Das Dr Vivek Arora Dr Anuj Gogi Dr Ketan Vijay Jathar Dr Ravi Rupsingh Dekate Dr Vanuli Bajpai (Medical Retina) Dr Vishal Mohan Rathore Dr Shalini Singh Dr Arvind Babu C (Uvea & Dr Ramana Kumar P J Dr M Nivean Medical retina) Dr G Sunil Dr Manavi D Sindal Dr Sudipta Das Dr Shormin Shohelly Shipa (Uvea Dr Maneesh M Bapayee Dr Daraius Shroff Dr Deepak Agarwal & Medical retina) Dr Pukhraj Rishi Dr Abhishek Ragunandan Kothari Dr Roopleen (Uvea & Medical Dr Rupak Kanti Biswas Dr V Jayaprakash Dr Madhusudan Dinesh Davda retina) Dr Unnikrishnan Nair Dr Bindu K Appukuttan Dr Subhankar Sri Pal Dr Renu Dhasmana Dr Arti Rupalia Pankaj Dr Aashraya Pritviraj Karpe Dr Aditya Verma Dr Pradeep Kumar Panigrahi Dr Aditi Gupta Dr V S Prakash (SNK) Dr Krishnendu Nandi Dr Kadri Venkatesh Dr K Nandakumar Dr Abhinandan N Patil Dr G Suganeswari Dr Anshul Goyal Dr Vikrant Sharma Dr Subha Laxmanan Dr Ankur Gupta Dr Aradhana Shriram Kadekar Dr Harshali Subhash Kamat Dr Ambatipudi Srinivas Dr Brahadeesh Subramaniam Dr Rajendra Kumar Thakur Dr Vishal Rajan Sharma Dr Chintamani Madhave Khare Dr Pallavi Gaurishankar Sarate Dr Sherran Raveendran Dr Balbir Khan Dr Jay Kumar Chhablani Dr Sayalee Tatyarao Lahane Dr Vishnu Suryaprakash Dr Cheriya Shane Mathew Dr Swagata Sarkar Dr Vishal Suresh Kakhandki Dr Himabindu Adusumilli Dr Sarita Shetty Dr Kumar Saurabh Dr Vishal V Kulkarani Dr Teena Agarwal Dr Anupama B (Medical Retina) Dr Sireesha Pasupuleti (Uvea & Dr.Sukanya A (Medical Retina) Dr Anshu Arora Dr Shah Bhavesh Jagadishkumar Medical retina) Dr Hemalatha B C Dr Manmath Kumar Das Dr Akash Patel (Medical Retina) Dr Deepak N Bhojwani Dr (MAJ) Sandeep Shankar Dr Shafiq Jafferji Dr Abhishek Dr Ruchi Juneja Dr Vimal Kundanmal Parmar Dr Jeepalem Sumanth Reddy Dr Barsha Sarma Dr Amol Ashok Wankhede Dr Manoj S Khatri Dr Sabyasachi Somnath Dr Debmalya Das (SNK) Dr Saban Horo Sengupta Dr Arshi Ahmed (Uvea & Medical Dr Sumeet Jain Dr Chinmaya Amulyanath Sahu Dr Md Arif Abdulrab Mulla retina) Dr Ashok Natarajan Dr Rupak Roy Dr Jaydeep Avinash Walinjkar Dr Sheshadri V Mahajan Dr Sudhir Gorakhnath Sudrik Dr Yogesh Devidas Patil Dr Abhishek Dixit Dr Shana Waz Kazi Dr Badami Nagaraj Kalpana Dr Nitish Mahajan Dr Pracheer Ranjan Agarwal Dr Shaileen Dushyantbhai Parikh Dr Prasad Anand Kamat Dr Subhajit Das Dr Swetha Palla (Uvea & Medical Dr Sharad Chandraprakash Rai Dr Vishal Agrawal Dr Sandhya Hegde retina) Dr Sarath Ravi Dr Amit Basia Dr Meenakshi V (Medical Retina) Dr Arindam Chakravarti Dr Shankaralakshmi (Uvea & Dr Aparna A C (Uvea & Medical Dr Chinmayi Vyas (Medical Dr Mayank Dutta Medical retina) Retina) Retina) Dr Tapas Ranjan Padhi Dr Narendran Muthukrishnan Dr Sukant Pandey Dr Anindya Kishor Majumder Dr R Vijayakumar Dr Hajee Hussein Frogh Dr Myna Achar (Medical Retina) (Uvea & Medical Retina, SNK) Shri Bhagwan Mahavir Vitreoretinal Services Sankara Nethralaya

Standing (Left to right): Dr. Vinata Muralidharan, Dr. Debamalya Das, Dr. Eesh Nigam, Dr. Mohammadarif Mulla, Dr. Vadivelu Jaya Prakash, Dr. Pukhraj Rishi, Dr. Pramod Bhende, Dr. Jaydeep Avinash Walinjkar, Dr. Rajesh P, Dr. Rajiv Raman, Dr. Aditya Verma

Sitting (Left to right): Dr. Parveen Sen, Dr. Chetan Rao, Dr. Muna Bhende, Dr. Vikas Khetan, Dr. Lingam Gopal, Dr. Pradeep Susvar, Dr. Tarun Sharma, Dr. Sukanya A, Dr. Suganeswari G, Dr. Veena Bhaskaran, Dr. Ekta Rishi